Vasodilator therapy is common in acute heart failure (AHF) patients, although evidence for morbidity and mortality benefits is limited for many of these drugs. AHF is frequently accompanied by renal dysfunction, which...Vasodilator therapy is common in acute heart failure (AHF) patients, although evidence for morbidity and mortality benefits is limited for many of these drugs. AHF is frequently accompanied by renal dysfunction, which is a strong, independent predictor for poor prognosis. Several hemodynamic and neurohormonal effects of vasodilators—including preload and afterload reduction, activation or inhibition of neurohormonal and inflammatory cascades—have the potential to modulate cardiorenal interaction and impact renal function. However, the effect of vasodilators on renal function in acute heart failure is often poorly described. In this review, we provide an overview of the known cardiorenal effects of traditional and novel vasodilators in patients with acute heart failure.展开更多
In this study,Ulva prolifera protein was used for preparing angiotensin-I converting enzyme(ACE)-inhibitory peptide via virtual gastrointestinal digestion and in silico screening.Some parameters of the obtained peptid...In this study,Ulva prolifera protein was used for preparing angiotensin-I converting enzyme(ACE)-inhibitory peptide via virtual gastrointestinal digestion and in silico screening.Some parameters of the obtained peptide,such as inhibition kinetics,docking mechanism,stability,transport pathway,were explored by Lineweaver-Burk plots,molecular docking,in vitro stimulate gastrointestinal(GI)digestion and Caco-2 cells monolayer model,respectively.Then,a novel anti-ACE peptide LDF(IC_(50),(1.66±0.34)μmol/L)was screened and synthesized by chemical synthesis.It was a no-competitive inhibitor and its anti-ACE inhibitory effect mainly attributable to four Conventional Hydrogen Bonds and Zn701 interactions.It could keep activity during simulated GI digestion in vitro and was transported by peptide transporter PepT1 and passive-mediated mode.Besides,it could activate Endothelial nitric oxide synthase(eNOS)activity to promote the production of NO and reduce Endothelin-1(ET-1)secretion induced by AngiotensinⅡ(AngⅡ)in Human Umbilical Vein Endothelial Cells(HUVECs).Meanwhile,it could promote mice splenocytes proliferation in a concentration-dependent manner.Our study indicated that this peptide was a potential ingredient functioning on vasodilation and enhancing immunity.展开更多
It has become increasingly apparent that the looming epidemic of heart failure calls for systematic treatment approaches tailored to the needs of individual patient phenotypes. Although chronic heart failure (CHF) the...It has become increasingly apparent that the looming epidemic of heart failure calls for systematic treatment approaches tailored to the needs of individual patient phenotypes. Although chronic heart failure (CHF) therapies are continuously evolving based on the increasing understanding of the involved etiology, acute heart failure (AHF) therapies are still based on hemodynamic improvements and symptom alleviation. Guidelines on AHF management have highlighted that the currently administered AHF therapies lack evidence and have raised concerns on the safety and efficacy of some of the hitherto accepted treatment modalities. Additionally, the high mortality and morbidity rates associated with the current AHF therapies also add to the imperative need to revisit AHF management. The last decade has witnessed a paradigm shift in the way we define and diagnose AHF. Apart from it being recognized as a distinct clinical entity, research has also led to new data on the pathophysiological changes associated with AHF. These developments along with the limited short- and long-term effects of currently used therapies may herald a paradigm shift in the way we plan and deliver management strategies to treat the pathological progression of heart failure.展开更多
Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmon...Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.展开更多
Aim: To report a case of longer-lived patent ductus arteriosus with features of pulmonary arterial hypertension up to the age of 65 years in an elderly woman. Introduction: The clinical recognition of patent ductus ar...Aim: To report a case of longer-lived patent ductus arteriosus with features of pulmonary arterial hypertension up to the age of 65 years in an elderly woman. Introduction: The clinical recognition of patent ductus arteriosus with severe pulmonary hypertension is difficult. Only 60% of adults presented with a continuous murmur in a recent series. Asymptomatic patent ductus arteriosus tolerated for many years and may not require closure. Case Report: A 65 years old female presented with dyspnea had signs of pulmonary arterial hypertension with enlarged pulmonary artery and its branches, atrial fibrillation along with a continuous murmur in the left second intercostal space. Echocardiography revealed a 13 mm size patent ductus arteriosus and a bidirectional with predominant left-to-right shunt. Patient was managed conservatively and symptoms got improved with medical therapy. Conclusion: Treatment of patent ductus arteriosus in the setting of pulmonary hypertension is challenging. Early repair can mitigate the development of pulmonary hypertension and reverse vasculopathy in more advanced disease. Maternal aspirin ingestion should be avoided in pregnancy since it causes constriction of fetal ductus.展开更多
Objective: The internal thoracic artery (ITA) is the conduit of choice for coronary artery bypass grafting (CABG). To avoid spasm of the ITA various topical vasodilators have been suggested either intraluminally or by...Objective: The internal thoracic artery (ITA) is the conduit of choice for coronary artery bypass grafting (CABG). To avoid spasm of the ITA various topical vasodilators have been suggested either intraluminally or by topical application. In order to describe the best vasodilating agent for preparation of the ITA, a randomized double-blind placebo controlled clinical work was performed in a group of CABG patients. Methods: Three hundred consecutive patients submitted for elective first time coronary artery bypass grafting were randomly subdivided into five groups. The first measurement was performed shortly after the internal thoracic artery was dissected from the chest wall and the second just prior to performing distal anastomosis to the left anterior descending coronary artery. During the time interval between the two measurements topical vasodilator has been injected into the endothoracic fascia of the ITA using the following drugs: papaverine 2 mg/ml, nitrogly-cerin 1 mg/ml, nitroprusside 0.5 mg/ml, mixed solution include sodium nitroprusside (1 mg/ml) and diltiazem (0.5 mg/ml) and normal saline 0.9%. Results: No statistically significant differences were found between the groups in respect to age, body surface area, cardiopulmonary bypass time, cross clamping time, and time interval between the two flow measurements. Mean arterial pressure at the time of the first and second internal thoracic artery flow measurements did not show statistically significant differences either within or between the groups. In all five groups, the free flow of the internal thoracic artery increased significantly with time. However, no statistically significant differences were shown between the five groups with respect to second flow. Conclusions: We suggest that preparation of the ITA by topical vasodilators injection into the endothoracic fascia does not result in a significantly superior free flow than placebo.展开更多
In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, m...In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.展开更多
Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expa...Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.展开更多
Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despit...Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.展开更多
AIM:To explore the role of heat shock protein-90 (HSP-90) for nitrergic vasorelaxation in the splanchnic circulation in rats with and without portal hypertension. METHODS: Neuronal nitric oxide synthase (nNOS) and HSP...AIM:To explore the role of heat shock protein-90 (HSP-90) for nitrergic vasorelaxation in the splanchnic circulation in rats with and without portal hypertension. METHODS: Neuronal nitric oxide synthase (nNOS) and HSP-90 were analyzed by immunofluorescence, western blotting and co-immunoprecipitation in the mesenteric vasculature and isolated nerves of portal-vein-ligated (PVL) rats and sham operated rats. In vitro perfused de-endothelialized mesenteric arterial vasculature was preconstricted with norepinephrine (EC80) and tested for nNOS-mediated vasorelaxation by periarterial nerve stimulation (PNS, 2-12 Hz, 45V) before and after incubation with geldanamycin (specific inhibitor of HSP-90 signalling, 3 μg/mL) or L-NAME (non-specific NOSblocker, 10-4 mol/L). RESULTS: nNOS and HSP-90 expression was significantly increased in mesenteric nerves from PVL as compared to sham rats. Moreover, nNOS and HSP-90 were visualized in mesenteric nerves by immunofluorescence and immunoprecipitation of nNOS co-immunoprecitated HSP-90 in sham and PVL rats. PNS induced a frequencydependent vasorelaxation which was more pronounced in PVL as compared to sham rats. L-NAME and geldanamycin markedly reduced nNOS-mediated vasorelaxation abrogating differences between the study groups. The effect of L-NAME and geldanamycin on nNOS-mediated vasorelaxation was significantly greater in PVL than in sham animals. However, no difference in magnitude of effect between L-NAME and geldanamycin was noted. CONCLUSION: HSP-90 acts as a signalling mediator of nNOS-dependent nerve mediated vascular responses in mesenteric arteries, and the increased nitrergic vasorelaxation observed in portal hypertension is mediated largely by HSP-90.展开更多
Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and...Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-KET-1) of the patients with cervical atherosclerosis. Methods: Forty patients were randomly divided into two groups; XSC group and Probucol group (western medicine control). In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results; Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P< 0. 01), NID also decreased (P<0. 05), the internal diameter of basal brachial artery has no obvious difference (P>0. 05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks, FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P<0.05, P<0.01), NID didn't change obviously (P>0.05). Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.展开更多
Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a...Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.展开更多
OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chin...OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.展开更多
Background: The magnitude of the hyperemic response due to repeated thigh stump exercise on incremental contraction intensity might be useful information in localized exercise tolerance for devising cardiovascular phy...Background: The magnitude of the hyperemic response due to repeated thigh stump exercise on incremental contraction intensity might be useful information in localized exercise tolerance for devising cardiovascular physical therapy for amputees. The effect of exercise on amputated leg blood flow (LBF) may potentially be altered due to voluntary muscle contractions after loss of the lower leg compared with the healthy leg. Case Presentation: A 57-year-old male patient with Burger disease attempted 3 min unilateral repeat/dynamic knee extensor exercise at a target muscle contraction frequency (1 s thigh muscle contraction and 1 s relaxation, 90 repetitions) with each leg <right transtibial amputated leg (AL) using a total surface-bearing prosthesis (TSB) and left non-AL> at six different contraction intensities (rubber resistance belt). Simultaneous measurement of blood velocity/flow (Doppler ultrasound) in the femoral artery, blood pressure, leg vascular conductance (LVC), and peak muscle strength (PMS) were performed during the 3 min exercise period. The maximum voluntary contraction by one-legged isometric knee muscle contraction was 14.7 kg in non-AL and 7.9 kg in the AL with prosthesis. The relative PMS was defined as “PMS/maximum voluntary contraction × 100 (%)”. Pre-exercise LBF was lower in the AL (200 ± 25 ml/min) than the non-AL (275 ± 74 ml/min). Both the non-AL and AL showed good positive linear relationships between absolute-/relative-PMS and LBF or LVC during 30 s at steady-state before the end of the exercise period. Furthermore, there was also similarity seen in the increase rate in LBF and/or LVC for the incremental relative PMS compared with the absolute PMS. Conclusion: In this case, the muscle strength depended on blood flow increase/vasodilation was seen in this “AL” using a TSB prosthesis for repeated dynamic knee extensor exercise. The present amputee’s limb muscle strengthening with the resection stump closely related to the degree of hyperemia in the amputated limb.展开更多
We present the case of a 65-year-old male with vasospastic angina(VSA)whose condition worsened during the perioperative period.He had been diagnosed with VSA 10 years prior.He was treated with two types of vasodilator...We present the case of a 65-year-old male with vasospastic angina(VSA)whose condition worsened during the perioperative period.He had been diagnosed with VSA 10 years prior.He was treated with two types of vasodilators and had not experienced any chest symptoms for 5 years.At this juncture,he underwent surgery for relapsed maxillary sublingual carcinoma.He had taken two vasodilators one day prior to surgery.Intravenous infusion of nitroglycerin(NTG)was initiated immediately before the surgery and continued the following day.Instead of stopping NTG,a dermal isosorbide dinitrate tape was applied on post-operative day 1.Two days later,a complete atrioventricular block with pulseless electrical activity appeared.After cardiopulmonary resuscitation,emergent coronary angiography showed severe coronary spasm in both the left and right coronary arteries.Intracoronary infusion of nitroglycerin and epinephrine with percutaneous cardiopulmonary support relieved the coronary spasm.During the perioperative period,several factors can trigger coronary vasospasm,including the discontinuation of vasodilators.Thus,surgeons,anesthetists,and cardiologists should watch for coronary vasospasm during this period and for worsening coronary spasm when discontinuing vasodilators in patients at risk for VSA.展开更多
Objective: To discover the mechanism behind ameliorative effects of Michelia champaca(M. champaca) in gastrointestinal, respiratory and cardiovascular disorders. Methods: Antispasmodic potential was evaluated by tryin...Objective: To discover the mechanism behind ameliorative effects of Michelia champaca(M. champaca) in gastrointestinal, respiratory and cardiovascular disorders. Methods: Antispasmodic potential was evaluated by trying the M. champaca extract(aqueous:ethanolic) on rabbit aorta, trachea and jejunum in vitro. Isotonic and isometric transducers coupled with Power Lab data acquisition system was used to record the responses of isolated tissues. Results: M. champaca extract relaxed the spontaneous and high K^+(80 mmol/L)-induced contractions of isolated jejunum preparation of rabbit showing a Ca^(2+) channel blocking mechanism. Moreover, extract shifted calcium concentration response curves towards right like standard calcium channel blocker verapamil. In rabbit tracheal preparation, M. champaca relaxed both carbachol(1 μmol/L) and high K^+-induced contractions, likewise verapamil. In rabbit aorta preparation, M. champaca relaxed phenylephrine(1 μmol/L) and high K^+-induced contractions similar to verapamil. Conclusion: M. champaca possesses spasmolytic, airways relaxant and vasodilator actions mediated perhaps due to blocking of Ca^(2+) channels, hence validating its therapeutic usage in diarrhea, asthma and hypertension.展开更多
Heart failure(HF) is a syndrome recognized as a health problem worldwide. Despite advances in treatment, patients with HF still have increased morbidity and mortality. Testosterone is one of the most researched hormon...Heart failure(HF) is a syndrome recognized as a health problem worldwide. Despite advances in treatment, patients with HF still have increased morbidity and mortality. Testosterone is one of the most researched hormones in the course of HF. Growing interest regarding the effect of testosterone, on a variety of body systems, has increased the knowledge about its mechanisms of action. The terms central and peripheral effects are used to distinguish the effects of testosterone on cardiac and extracardiac structures. Central effects include influences on cardiomyocytes and electrophysiology. Peripheral effects include influences on blood vessels, baroreceptor reactivity, skeletal muscles and erythropoesis. Current knowledge about peripheral effects of testosterone may explain much about beneficiary effects in the pathophysiology of HF syndrome. However, central, i.e., cardiac effects of testosterone are to be further explored.展开更多
To examine the role of nitric oxide in the β-adrenergic vasodilation of epicardial coronary arteries in dogs, 12 dogs were instrumented for measurement of left anterior descending coronary artery diameter by transtho...To examine the role of nitric oxide in the β-adrenergic vasodilation of epicardial coronary arteries in dogs, 12 dogs were instrumented for measurement of left anterior descending coronary artery diameter by transthoracic echocardiography before and after dobutamine (5 μg/kg/min IV) with and without intracoronary infusion of N G-monomethyl-L-arginine (L-NMMA) (1 mg/kg). In all 12 dogs, the diameter of left anterior descending coronary artery increased significantly from 2.35±0.25 mm to 2.59±0.24 mm (P<0.001) after dobutamine administration. In 6 of the 12 dogs, the percent change in left anterior descending coronary artery diameter induced by dobutamine decreased significantly from 12.5%±8.6% to -1.5%±5.4% (P<0.05) after the administration of intracoronary L-NMMA (1 mg/kg for 5 min) to block nitric oxide synthesis from L-arginine. The study demonstrated that nitric oxide formation contributes to the β-adrenergic dilatory response of epicardial coronary arteries to dobutamine in dogs.展开更多
AIM:To investigate if significant improvement of optic disc blood flow(ODBF) occurs after instillation of brinzolamide onto rabbit eyes.METHODS:Testing of bilateral intraocular pressure(IOP) and left ODBF in 10 ...AIM:To investigate if significant improvement of optic disc blood flow(ODBF) occurs after instillation of brinzolamide onto rabbit eyes.METHODS:Testing of bilateral intraocular pressure(IOP) and left ODBF in 10 male rabbits took place every 3 h over a 24 h period.Brinzolamide(1% ophthalmic solution,two drops at 9:00 and 21:00) was administered to the left eye.ODBF,assessed using laser speckle flowgraphy,was determined as the mean blur rate(MBR).Furthermore,the effect of brinzolamide on isolated rabbit ciliary arteries using isometric tension recording system was performed.RESULTS:After brinzolamide instillation,IOP was significantly decreased in the left eye.MBR-vessel was greater at 18:00 and 21:00(P〈0.05) than in the controls.MBRtissue and MBR-average were greater at 18:00(P〈0.05) than in the controls.For isolated arteries pre-contracted with a high-K solution,brinzolamide induced concentration-dependent relaxation,reaching 46.1%±9%(n=21) at 1 mmol/L.In Ca^2+-free solutions,incubation with brinzolamide suppressed 1 μmol/L histamine-induced contractions(P〈0.05).CONCLUSION:Brinzolamide decreases IOP and increases ocular blood flow.The direct vasodilatory effect of brizolamide is mediated by suppression of Ca^2+ release from intracellular calcium stores.展开更多
Study was carried out in rabbits to determine whether 3,4’,5-trihydroxystibene-3-β-nono-D-glucoside(PD)has wasodilative action using volumetric method.The result showed PD(1.71 mol/L)caused a right shift of the cumu...Study was carried out in rabbits to determine whether 3,4’,5-trihydroxystibene-3-β-nono-D-glucoside(PD)has wasodilative action using volumetric method.The result showed PD(1.71 mol/L)caused a right shift of the cumulative concentration-reponse curve of uorepinephfine(NE)and lowered the maximal response of rabbit’s pulmonary arteries.It implies that PD couldinhibit the vasoconstfictive effect of NE in a noncompetitive manner.PD dilated the pulmonaryarteries(4.09 and 5.12mmol/L)and the carotid(5.12mmol/L)of rabbits.This PD-induced relax-ation of puhnonary artenes was weakened by propranolol(87.8μmol/L).展开更多
文摘Vasodilator therapy is common in acute heart failure (AHF) patients, although evidence for morbidity and mortality benefits is limited for many of these drugs. AHF is frequently accompanied by renal dysfunction, which is a strong, independent predictor for poor prognosis. Several hemodynamic and neurohormonal effects of vasodilators—including preload and afterload reduction, activation or inhibition of neurohormonal and inflammatory cascades—have the potential to modulate cardiorenal interaction and impact renal function. However, the effect of vasodilators on renal function in acute heart failure is often poorly described. In this review, we provide an overview of the known cardiorenal effects of traditional and novel vasodilators in patients with acute heart failure.
文摘In this study,Ulva prolifera protein was used for preparing angiotensin-I converting enzyme(ACE)-inhibitory peptide via virtual gastrointestinal digestion and in silico screening.Some parameters of the obtained peptide,such as inhibition kinetics,docking mechanism,stability,transport pathway,were explored by Lineweaver-Burk plots,molecular docking,in vitro stimulate gastrointestinal(GI)digestion and Caco-2 cells monolayer model,respectively.Then,a novel anti-ACE peptide LDF(IC_(50),(1.66±0.34)μmol/L)was screened and synthesized by chemical synthesis.It was a no-competitive inhibitor and its anti-ACE inhibitory effect mainly attributable to four Conventional Hydrogen Bonds and Zn701 interactions.It could keep activity during simulated GI digestion in vitro and was transported by peptide transporter PepT1 and passive-mediated mode.Besides,it could activate Endothelial nitric oxide synthase(eNOS)activity to promote the production of NO and reduce Endothelin-1(ET-1)secretion induced by AngiotensinⅡ(AngⅡ)in Human Umbilical Vein Endothelial Cells(HUVECs).Meanwhile,it could promote mice splenocytes proliferation in a concentration-dependent manner.Our study indicated that this peptide was a potential ingredient functioning on vasodilation and enhancing immunity.
文摘It has become increasingly apparent that the looming epidemic of heart failure calls for systematic treatment approaches tailored to the needs of individual patient phenotypes. Although chronic heart failure (CHF) therapies are continuously evolving based on the increasing understanding of the involved etiology, acute heart failure (AHF) therapies are still based on hemodynamic improvements and symptom alleviation. Guidelines on AHF management have highlighted that the currently administered AHF therapies lack evidence and have raised concerns on the safety and efficacy of some of the hitherto accepted treatment modalities. Additionally, the high mortality and morbidity rates associated with the current AHF therapies also add to the imperative need to revisit AHF management. The last decade has witnessed a paradigm shift in the way we define and diagnose AHF. Apart from it being recognized as a distinct clinical entity, research has also led to new data on the pathophysiological changes associated with AHF. These developments along with the limited short- and long-term effects of currently used therapies may herald a paradigm shift in the way we plan and deliver management strategies to treat the pathological progression of heart failure.
文摘Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.
文摘Aim: To report a case of longer-lived patent ductus arteriosus with features of pulmonary arterial hypertension up to the age of 65 years in an elderly woman. Introduction: The clinical recognition of patent ductus arteriosus with severe pulmonary hypertension is difficult. Only 60% of adults presented with a continuous murmur in a recent series. Asymptomatic patent ductus arteriosus tolerated for many years and may not require closure. Case Report: A 65 years old female presented with dyspnea had signs of pulmonary arterial hypertension with enlarged pulmonary artery and its branches, atrial fibrillation along with a continuous murmur in the left second intercostal space. Echocardiography revealed a 13 mm size patent ductus arteriosus and a bidirectional with predominant left-to-right shunt. Patient was managed conservatively and symptoms got improved with medical therapy. Conclusion: Treatment of patent ductus arteriosus in the setting of pulmonary hypertension is challenging. Early repair can mitigate the development of pulmonary hypertension and reverse vasculopathy in more advanced disease. Maternal aspirin ingestion should be avoided in pregnancy since it causes constriction of fetal ductus.
文摘Objective: The internal thoracic artery (ITA) is the conduit of choice for coronary artery bypass grafting (CABG). To avoid spasm of the ITA various topical vasodilators have been suggested either intraluminally or by topical application. In order to describe the best vasodilating agent for preparation of the ITA, a randomized double-blind placebo controlled clinical work was performed in a group of CABG patients. Methods: Three hundred consecutive patients submitted for elective first time coronary artery bypass grafting were randomly subdivided into five groups. The first measurement was performed shortly after the internal thoracic artery was dissected from the chest wall and the second just prior to performing distal anastomosis to the left anterior descending coronary artery. During the time interval between the two measurements topical vasodilator has been injected into the endothoracic fascia of the ITA using the following drugs: papaverine 2 mg/ml, nitrogly-cerin 1 mg/ml, nitroprusside 0.5 mg/ml, mixed solution include sodium nitroprusside (1 mg/ml) and diltiazem (0.5 mg/ml) and normal saline 0.9%. Results: No statistically significant differences were found between the groups in respect to age, body surface area, cardiopulmonary bypass time, cross clamping time, and time interval between the two flow measurements. Mean arterial pressure at the time of the first and second internal thoracic artery flow measurements did not show statistically significant differences either within or between the groups. In all five groups, the free flow of the internal thoracic artery increased significantly with time. However, no statistically significant differences were shown between the five groups with respect to second flow. Conclusions: We suggest that preparation of the ITA by topical vasodilators injection into the endothoracic fascia does not result in a significantly superior free flow than placebo.
基金Supported by the Grants from the Ministerio de Educacióny Ciencia, No. SAF2006-0314the Ministerio de Cienciae Innovación, No. SAF2009-08354
文摘In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.
文摘Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.
基金Supported by the European Social Fund and Scottish Funding Council as part of Developing Scotland’s Workforce in the Scotland 2014-2020 European Structural and Investment Fund Programme
文摘Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting.
基金Supported by Grants from the German Research Association (DFG) to Wiest R
文摘AIM:To explore the role of heat shock protein-90 (HSP-90) for nitrergic vasorelaxation in the splanchnic circulation in rats with and without portal hypertension. METHODS: Neuronal nitric oxide synthase (nNOS) and HSP-90 were analyzed by immunofluorescence, western blotting and co-immunoprecipitation in the mesenteric vasculature and isolated nerves of portal-vein-ligated (PVL) rats and sham operated rats. In vitro perfused de-endothelialized mesenteric arterial vasculature was preconstricted with norepinephrine (EC80) and tested for nNOS-mediated vasorelaxation by periarterial nerve stimulation (PNS, 2-12 Hz, 45V) before and after incubation with geldanamycin (specific inhibitor of HSP-90 signalling, 3 μg/mL) or L-NAME (non-specific NOSblocker, 10-4 mol/L). RESULTS: nNOS and HSP-90 expression was significantly increased in mesenteric nerves from PVL as compared to sham rats. Moreover, nNOS and HSP-90 were visualized in mesenteric nerves by immunofluorescence and immunoprecipitation of nNOS co-immunoprecitated HSP-90 in sham and PVL rats. PNS induced a frequencydependent vasorelaxation which was more pronounced in PVL as compared to sham rats. L-NAME and geldanamycin markedly reduced nNOS-mediated vasorelaxation abrogating differences between the study groups. The effect of L-NAME and geldanamycin on nNOS-mediated vasorelaxation was significantly greater in PVL than in sham animals. However, no difference in magnitude of effect between L-NAME and geldanamycin was noted. CONCLUSION: HSP-90 acts as a signalling mediator of nNOS-dependent nerve mediated vascular responses in mesenteric arteries, and the increased nitrergic vasorelaxation observed in portal hypertension is mediated largely by HSP-90.
文摘Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-KET-1) of the patients with cervical atherosclerosis. Methods: Forty patients were randomly divided into two groups; XSC group and Probucol group (western medicine control). In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results; Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P< 0. 01), NID also decreased (P<0. 05), the internal diameter of basal brachial artery has no obvious difference (P>0. 05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks, FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P<0.05, P<0.01), NID didn't change obviously (P>0.05). Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.
文摘Recent evidence suggests that the condition of the gut and its microbiota greatly influence the course of liver disease,especially cirrhosis.This introduces the concept of the gut-liver axis,which can be imagined as a chain connected by several links.Gut dysbiosis,small intestinal bacterial overgrowth,and intestinal barrier alteration lead to bacterial translocation,resulting in systemic inflammation.Systemic inflammation further causes vasodilation,arterial hypotension,and hyperdynamic circulation,leading to the aggravation of portal hypertension,which contributes to the development of complications of cirrhosis,resulting in a poorer prognosis.The majority of the data underlying this model were obtained initially from animal experiments,and most of these correlations were further reproduced in studies including patients with cirrhosis.However,despite the published data on the relationship of the disorders of the gut microbiota with the complications of cirrhosis and the proposed pathogenetic role of hemodynamic disorders in their development,the direct relations between gut dysbiosis and hemodynamic changes in this disease are poorly studied.They remain a missing link in the gut-liver axis and a challenge for future research.
基金The project supported by Major Scientific and Technological Special Project for "Significant New Drug Creation"(2013ZX09508104,2013ZX09402203)by Central Public Scientific Research Institution Fundamental Project(2014CX05)
文摘OBJECTIVE To investigate the cerebralvasorelaxant material basis of Xiaoxuming decoction.METHODS According to the Xiaoxuming decoction herb sources,we retrieved the chemical structure from the literatures and the Chinese Natural Product Database(http://pharmdata.ncmi.cn).By using microvessel tension system,we checked the vasorelaxanteffects of Xiaoxuming decoction anti-cerebral ischemia effective components group(XXMDECG)and the available composition compounds on pre-contracted basilar artery ring.RESULTS963 compoundsin the decoction,including 81Fangfeng,77 Mahuang,130 Shengjiang,31 Guizhi,91 Huangqin,127 Renshen,73 Chuanxiong,44 Shaoyao,39 Xingren,42 Fangji,62 Fuzi and 166 Gancao were collected.The five largest number classes of compounds in the decoction are volatile oil(32%),flavone(32%),alkaloid(13%),saponin(7%),polyphenol and organic acid(5%).XXMDECG at concentration from 1 to 400μg·mL-1can dilate the KCl(60 mmol·L-1)and ET-1(0.01μmol·L-1)pre-contracted rat basilar artery rings in a dose-dependent manner.There are 6 compounds with vasorelaxant ratio more than 50%at the concentration of 10μmol·L-1.CONCLUSION Xiaoxuming decoction contains abundant chemical structure.It has the material basis of multiple ingredients and multiple targets.The XXMDECG are able to dilate the rat basilar artery rings in a dose-dependent manner.The network interactions between varies of chemical compounds in Xiaoxuming decoction and the vasoconstriction associated targets result in the comprehensive regulation mechanisms of vascular function.
文摘Background: The magnitude of the hyperemic response due to repeated thigh stump exercise on incremental contraction intensity might be useful information in localized exercise tolerance for devising cardiovascular physical therapy for amputees. The effect of exercise on amputated leg blood flow (LBF) may potentially be altered due to voluntary muscle contractions after loss of the lower leg compared with the healthy leg. Case Presentation: A 57-year-old male patient with Burger disease attempted 3 min unilateral repeat/dynamic knee extensor exercise at a target muscle contraction frequency (1 s thigh muscle contraction and 1 s relaxation, 90 repetitions) with each leg <right transtibial amputated leg (AL) using a total surface-bearing prosthesis (TSB) and left non-AL> at six different contraction intensities (rubber resistance belt). Simultaneous measurement of blood velocity/flow (Doppler ultrasound) in the femoral artery, blood pressure, leg vascular conductance (LVC), and peak muscle strength (PMS) were performed during the 3 min exercise period. The maximum voluntary contraction by one-legged isometric knee muscle contraction was 14.7 kg in non-AL and 7.9 kg in the AL with prosthesis. The relative PMS was defined as “PMS/maximum voluntary contraction × 100 (%)”. Pre-exercise LBF was lower in the AL (200 ± 25 ml/min) than the non-AL (275 ± 74 ml/min). Both the non-AL and AL showed good positive linear relationships between absolute-/relative-PMS and LBF or LVC during 30 s at steady-state before the end of the exercise period. Furthermore, there was also similarity seen in the increase rate in LBF and/or LVC for the incremental relative PMS compared with the absolute PMS. Conclusion: In this case, the muscle strength depended on blood flow increase/vasodilation was seen in this “AL” using a TSB prosthesis for repeated dynamic knee extensor exercise. The present amputee’s limb muscle strengthening with the resection stump closely related to the degree of hyperemia in the amputated limb.
文摘We present the case of a 65-year-old male with vasospastic angina(VSA)whose condition worsened during the perioperative period.He had been diagnosed with VSA 10 years prior.He was treated with two types of vasodilators and had not experienced any chest symptoms for 5 years.At this juncture,he underwent surgery for relapsed maxillary sublingual carcinoma.He had taken two vasodilators one day prior to surgery.Intravenous infusion of nitroglycerin(NTG)was initiated immediately before the surgery and continued the following day.Instead of stopping NTG,a dermal isosorbide dinitrate tape was applied on post-operative day 1.Two days later,a complete atrioventricular block with pulseless electrical activity appeared.After cardiopulmonary resuscitation,emergent coronary angiography showed severe coronary spasm in both the left and right coronary arteries.Intracoronary infusion of nitroglycerin and epinephrine with percutaneous cardiopulmonary support relieved the coronary spasm.During the perioperative period,several factors can trigger coronary vasospasm,including the discontinuation of vasodilators.Thus,surgeons,anesthetists,and cardiologists should watch for coronary vasospasm during this period and for worsening coronary spasm when discontinuing vasodilators in patients at risk for VSA.
文摘Objective: To discover the mechanism behind ameliorative effects of Michelia champaca(M. champaca) in gastrointestinal, respiratory and cardiovascular disorders. Methods: Antispasmodic potential was evaluated by trying the M. champaca extract(aqueous:ethanolic) on rabbit aorta, trachea and jejunum in vitro. Isotonic and isometric transducers coupled with Power Lab data acquisition system was used to record the responses of isolated tissues. Results: M. champaca extract relaxed the spontaneous and high K^+(80 mmol/L)-induced contractions of isolated jejunum preparation of rabbit showing a Ca^(2+) channel blocking mechanism. Moreover, extract shifted calcium concentration response curves towards right like standard calcium channel blocker verapamil. In rabbit tracheal preparation, M. champaca relaxed both carbachol(1 μmol/L) and high K^+-induced contractions, likewise verapamil. In rabbit aorta preparation, M. champaca relaxed phenylephrine(1 μmol/L) and high K^+-induced contractions similar to verapamil. Conclusion: M. champaca possesses spasmolytic, airways relaxant and vasodilator actions mediated perhaps due to blocking of Ca^(2+) channels, hence validating its therapeutic usage in diarrhea, asthma and hypertension.
文摘Heart failure(HF) is a syndrome recognized as a health problem worldwide. Despite advances in treatment, patients with HF still have increased morbidity and mortality. Testosterone is one of the most researched hormones in the course of HF. Growing interest regarding the effect of testosterone, on a variety of body systems, has increased the knowledge about its mechanisms of action. The terms central and peripheral effects are used to distinguish the effects of testosterone on cardiac and extracardiac structures. Central effects include influences on cardiomyocytes and electrophysiology. Peripheral effects include influences on blood vessels, baroreceptor reactivity, skeletal muscles and erythropoesis. Current knowledge about peripheral effects of testosterone may explain much about beneficiary effects in the pathophysiology of HF syndrome. However, central, i.e., cardiac effects of testosterone are to be further explored.
基金supported by a grant from the National Natura1 Science Foundation of China(No.30270560).
文摘To examine the role of nitric oxide in the β-adrenergic vasodilation of epicardial coronary arteries in dogs, 12 dogs were instrumented for measurement of left anterior descending coronary artery diameter by transthoracic echocardiography before and after dobutamine (5 μg/kg/min IV) with and without intracoronary infusion of N G-monomethyl-L-arginine (L-NMMA) (1 mg/kg). In all 12 dogs, the diameter of left anterior descending coronary artery increased significantly from 2.35±0.25 mm to 2.59±0.24 mm (P<0.001) after dobutamine administration. In 6 of the 12 dogs, the percent change in left anterior descending coronary artery diameter induced by dobutamine decreased significantly from 12.5%±8.6% to -1.5%±5.4% (P<0.05) after the administration of intracoronary L-NMMA (1 mg/kg for 5 min) to block nitric oxide synthesis from L-arginine. The study demonstrated that nitric oxide formation contributes to the β-adrenergic dilatory response of epicardial coronary arteries to dobutamine in dogs.
基金Supported by Japan Society for the Promotion of Science(JSPS) Grant-in-Aid for Scientific Research(C)(No.25462750)
文摘AIM:To investigate if significant improvement of optic disc blood flow(ODBF) occurs after instillation of brinzolamide onto rabbit eyes.METHODS:Testing of bilateral intraocular pressure(IOP) and left ODBF in 10 male rabbits took place every 3 h over a 24 h period.Brinzolamide(1% ophthalmic solution,two drops at 9:00 and 21:00) was administered to the left eye.ODBF,assessed using laser speckle flowgraphy,was determined as the mean blur rate(MBR).Furthermore,the effect of brinzolamide on isolated rabbit ciliary arteries using isometric tension recording system was performed.RESULTS:After brinzolamide instillation,IOP was significantly decreased in the left eye.MBR-vessel was greater at 18:00 and 21:00(P〈0.05) than in the controls.MBRtissue and MBR-average were greater at 18:00(P〈0.05) than in the controls.For isolated arteries pre-contracted with a high-K solution,brinzolamide induced concentration-dependent relaxation,reaching 46.1%±9%(n=21) at 1 mmol/L.In Ca^2+-free solutions,incubation with brinzolamide suppressed 1 μmol/L histamine-induced contractions(P〈0.05).CONCLUSION:Brinzolamide decreases IOP and increases ocular blood flow.The direct vasodilatory effect of brizolamide is mediated by suppression of Ca^2+ release from intracellular calcium stores.
基金This project was supprted by the Natonal Natural Science Foundation of China No 3880738
文摘Study was carried out in rabbits to determine whether 3,4’,5-trihydroxystibene-3-β-nono-D-glucoside(PD)has wasodilative action using volumetric method.The result showed PD(1.71 mol/L)caused a right shift of the cumulative concentration-reponse curve of uorepinephfine(NE)and lowered the maximal response of rabbit’s pulmonary arteries.It implies that PD couldinhibit the vasoconstfictive effect of NE in a noncompetitive manner.PD dilated the pulmonaryarteries(4.09 and 5.12mmol/L)and the carotid(5.12mmol/L)of rabbits.This PD-induced relax-ation of puhnonary artenes was weakened by propranolol(87.8μmol/L).