Nicotinamide adenine dinucleotide (NADH/NAD+) is involved in important biochemical reactions in human metabolism, including participation in energy production by mitochondria. The changes in fluorescence intensity as ...Nicotinamide adenine dinucleotide (NADH/NAD+) is involved in important biochemical reactions in human metabolism, including participation in energy production by mitochondria. The changes in fluorescence intensity as a function of time in response to blocking and releasing of blood flow in a forearm are used as a measure of oxygen transport with blood to the tissue, which directly correlates with the skin microcirculation status. In this paper, a non-invasive dynamic monitoring system based on blood flow-mediated skin fluorescence (FMSF) technology is developed to monitor the NADH fluorescence intensity of skin tissue during the process of blocking reactive hyperemia. Simultaneously, laser speckle contrast imaging (LSCI) and laser Doppler flowmetry (LDF) were used to observe blood flow, blood oxygen saturation (SOt2) and relative amount of hemoglobin (rHb) during the measurement process, which helped to explore NADH dynamics relevant physiological changes. A variety of parameters have been derived to describe NADH fluorescence curve based on the FMSF device. The experimental results are conducive to understanding the NADH measurement and the physiological processes related to it, which help FMSF to be a great avenue for in vivo physiological, clinical and pharmacological research on mitochondrial metabolism.展开更多
Objectives: To evaluate the association of diastolic function of the left ventricle with flowme-diated dilatation (FMD) in uncomplicated Type 2 diabetes mellitus patients. Methods: Eighty-two uncomplicated Type 2 diab...Objectives: To evaluate the association of diastolic function of the left ventricle with flowme-diated dilatation (FMD) in uncomplicated Type 2 diabetes mellitus patients. Methods: Eighty-two uncomplicated Type 2 diabetic patients were examined by pulse and tissue Doppler echocardiography and FMD of brachial artery. The patients were divided into 2 groups according to the size of the left ventricular relaxation parameter—E’. Results: The average age of the patients was 61 ± 6 years. FMD was 5.0 ± 1.8% in 41 patients with E’ from 3 to 7.4 cm/s (mean 6 cm/s) comparing to 5.1 ± 1.9% (p = 0.96) in 41 patients with E’ from 7.5 to 10.9 cm/s (mean 8.9 cm/s). E/E’ was 11.2 ± 2.3 in the group with lower E’ and 9.1 ± 1.6 in the group with higher E’ (p 0.001). Linear negative correlation was found between E/E’ and FMD for the patients with E’ from 3 to 7.4 cm/s (R2 = 0.131;p = 0.025) but not for the group of patients with the higher E’. The significant association between FMD and E/E’ was confirmed by multivariate analysis ((Rc)2 = 0.233;p 0.05). Conclusion: FMD has no impact on the left ventricular relaxation. However FMD is negatively associated with E/E’ in Type 2 diabetic patients who have low E’ as a sign of an impaired early relaxation.展开更多
In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-ind...In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-induced platelet aggregation.The present paper revealed that RG- DS had vasodilative action and the cGMP accumulation may be one of the mechanisms of RGDS exer- ting bioactivities.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
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
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
Background: The production of endothelial-derived factors induces either vasoconstriction or vasodilation;nitric oxide (NO) is the most distinguished relaxing factor. Endothelial dysfunction is associated with hyperte...Background: The production of endothelial-derived factors induces either vasoconstriction or vasodilation;nitric oxide (NO) is the most distinguished relaxing factor. Endothelial dysfunction is associated with hypertension. The partial loss in the NO-promoted vasodilation is due to its decreased bioavailability and/or to an activity reduction of endothelium NO synthase (eNOS). Reactive oxygen species (ROS), present in oxidative stress, seize NO and diminish its bioavailability. Transresveratrol (RESV) has been proved to increase NO and eNOS levels. Thus, RESV could be capable of improving NO dependent vascular relaxation on aortic rings isolated from treated 2K-1C animals through ROS damage reduction. Aim: Evaluate the effects of RESV treatment on the relaxation of aortic rings isolated from treated 2K-1C rats while focusing on the effects of the treatment on systolic blood pressure. Methods: Male Wistar rats (180 g) were grouped: two 2K-1C and two Sham groups, one of each was treated with RESV (20 mg/kg, gavage) dissolved in Tween 80 and one of each was treated with water plus Tween 80 (control) for six weeks. The rats had their systolic blood pressure (SBP) measured before and after the treatments. Vascular reactivity studies were conducted in order to observe and compare acetylcholine (ACh)-induced relaxations in the presence and absence of the NOS inhibitor L-NAME (10-4 mol/L). Results: SBP for 2K-1C was significantly reduced in the treated group (179.13 ± 4.90 mmHg, n = 23) when compared to the untreated group (196.66 ± 6.06 mmHg, n = 15, p < 0.01). The maximum relaxation of aortic rings isolated from the 2K-1C treated group showed a higher efficacy (116.63% ± 1.72%, n = 12) than that from the untreated group (85.97% ± 0.69%, n = 6, p < 0.001);L-NAME exposure was responsible for a significant decrease in each group’s maximum relaxation efficacy. Conclusions: SBP reduction observed after RESV treatment in rat renal hypertension could be due to the reestablishment of vascular relaxation depend of NO.展开更多
The binding of Fgn to GPIIb / IIIa has confirmed that there are two distinct amino acid sequences within the Fgn molecule that are responsible for mediating its attachment to GP IIb / IIIa receptor. In addition to mon...The binding of Fgn to GPIIb / IIIa has confirmed that there are two distinct amino acid sequences within the Fgn molecule that are responsible for mediating its attachment to GP IIb / IIIa receptor. In addition to monoclonal antibodies, the binding function of GP IIb / IIIa can be blocked by synthetic small peptides containing the RGD and APLRV sequence. In our preliminary study it was found that besides inhibition of platelet aggregation and thrombus formation RGDS showed vasodilation effects as well. In an attempt to confirm the vasodilation effect of RGDS related peptides, RGDF, APLRV, APLRVRGDS and APLRVRGDF were investigated. The effects of these synthetic peptides on rat aortic strips pretreated with NE in vitro were observed. The relaxing extents of contracted strips for the peptides at three doses (10 5 mol / L, 10 6 mol / L and 10 7 mol / L) were recorded.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
Background: Many factors can contribute to atherosclerotic-type vascular changes in older individuals or men. Thus, confining the investigation to young women with no clinical evidence of the condition could enhance u...Background: Many factors can contribute to atherosclerotic-type vascular changes in older individuals or men. Thus, confining the investigation to young women with no clinical evidence of the condition could enhance understanding of the early stages of cardiovascular disease. The aim of this study was to determine whether carotid mean/max intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) values, which are well-known event-related indices, are associated with laboratory data and the other vascular indices of atherosclerosis in healthy young women. Methods: Carotid mean/max IMT and brachial FMD were measured in young women with no clinical evidence of atherosclerosis (n = 110;mean age, 39 years) who were instructed not to eat, drink or smoke after 9 PM the evening before testing. All participants also underwent laboratory assessment, including simultaneous measurements of arterial stiffness such as augmentation index (AI), cardioankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). Results: Mean IMT was signifi-cantly and positively associated with age (p = 0.002), CAVI (p = 0.044), low-density lipoprotein-cholesterol (LDL-C, p = 0.047) and high-sensitive C-reactive protein (hs-CRP, p = 0.002) values but was not related to FMD, AI, baPWV or triglycerides (TG) in the multivariate regression analysis. Similarly, max IMT was positively associated with age (p p = 0.003) and hs-CRP (p = 0.005) values but was not related to FMD, AI, CAVI, baPWV, TG or blood pressure level in the multivariate regression analysis. The association between LDL-C and max IMT was much stronger than that between LDL-C and mean IMT. Brachial FMD was positively associated only with heart rate in the multivariate regression analysis. Conclusions: These results suggest that mean IMT more closely represents the sclerotic aspect of vascular change, whereas max IMT represents the atherotic aspect in healthy young women. Although the relationship between the autonomic nervous system and heart rate is well-known, there may be a complex interaction between the autonomic nervous system and endothelial function.展开更多
A series of new 2 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines and 3 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines have been synthesized. These derivatives were evaluated for inhibitory effects on...A series of new 2 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines and 3 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines have been synthesized. These derivatives were evaluated for inhibitory effects on 85 7 mmol·L 1 K + and 10 4 mmol·L -1 NE (nor epinephrine) induced contraction of rat aorta strips.展开更多
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
Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impa...Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impaired endothelial function has been observed in patients with CAD and those with CAD risk factors. Studies have shown that exercise can enhance endothelial function. Methods: This experimental cross-sectional study was conducted on patients with CAD (3 months after CABG and PCI) and students of medical school in 2011. Endothelium dependent dilation of the brachial artery was determined by using high-resolution vascular ultrasonography through flow-mediated vasodilatation (FMD) after induction of ischemia, and the data were analyzed using SPSS, dependent t-test and ANCOVA. Findings: The findings showed that at baseline, FMD was reduced in revascularized patients, when compared with healthy young men, after 8 weeks, and exercise training significantly improved FMD in patients underwent training group [from 4.31 ± 1.45 (SD)% to 6.15 ± 0.773 (SD)%, p p ed unchanged, and even after aerobic training, it did not significantly modify the brachial artery diameter in these groups. Conclusion: Our study demonstrates that endothelial dysfunction persisting in CAD patients after revascularization and aerobic training can improve endothelial function in different vascular beds in CAD patients and healthy young men. This may contribute to the benefit of regular exercise in preventing and restricting cardiovascular disease.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
文摘Nicotinamide adenine dinucleotide (NADH/NAD+) is involved in important biochemical reactions in human metabolism, including participation in energy production by mitochondria. The changes in fluorescence intensity as a function of time in response to blocking and releasing of blood flow in a forearm are used as a measure of oxygen transport with blood to the tissue, which directly correlates with the skin microcirculation status. In this paper, a non-invasive dynamic monitoring system based on blood flow-mediated skin fluorescence (FMSF) technology is developed to monitor the NADH fluorescence intensity of skin tissue during the process of blocking reactive hyperemia. Simultaneously, laser speckle contrast imaging (LSCI) and laser Doppler flowmetry (LDF) were used to observe blood flow, blood oxygen saturation (SOt2) and relative amount of hemoglobin (rHb) during the measurement process, which helped to explore NADH dynamics relevant physiological changes. A variety of parameters have been derived to describe NADH fluorescence curve based on the FMSF device. The experimental results are conducive to understanding the NADH measurement and the physiological processes related to it, which help FMSF to be a great avenue for in vivo physiological, clinical and pharmacological research on mitochondrial metabolism.
文摘Objectives: To evaluate the association of diastolic function of the left ventricle with flowme-diated dilatation (FMD) in uncomplicated Type 2 diabetes mellitus patients. Methods: Eighty-two uncomplicated Type 2 diabetic patients were examined by pulse and tissue Doppler echocardiography and FMD of brachial artery. The patients were divided into 2 groups according to the size of the left ventricular relaxation parameter—E’. Results: The average age of the patients was 61 ± 6 years. FMD was 5.0 ± 1.8% in 41 patients with E’ from 3 to 7.4 cm/s (mean 6 cm/s) comparing to 5.1 ± 1.9% (p = 0.96) in 41 patients with E’ from 7.5 to 10.9 cm/s (mean 8.9 cm/s). E/E’ was 11.2 ± 2.3 in the group with lower E’ and 9.1 ± 1.6 in the group with higher E’ (p 0.001). Linear negative correlation was found between E/E’ and FMD for the patients with E’ from 3 to 7.4 cm/s (R2 = 0.131;p = 0.025) but not for the group of patients with the higher E’. The significant association between FMD and E/E’ was confirmed by multivariate analysis ((Rc)2 = 0.233;p 0.05). Conclusion: FMD has no impact on the left ventricular relaxation. However FMD is negatively associated with E/E’ in Type 2 diabetic patients who have low E’ as a sign of an impaired early relaxation.
基金This project was supported by the National Natural Science Foundation
文摘In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-induced platelet aggregation.The present paper revealed that RG- DS had vasodilative action and the cGMP accumulation may be one of the mechanisms of RGDS exer- ting bioactivities.
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.
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Background: The production of endothelial-derived factors induces either vasoconstriction or vasodilation;nitric oxide (NO) is the most distinguished relaxing factor. Endothelial dysfunction is associated with hypertension. The partial loss in the NO-promoted vasodilation is due to its decreased bioavailability and/or to an activity reduction of endothelium NO synthase (eNOS). Reactive oxygen species (ROS), present in oxidative stress, seize NO and diminish its bioavailability. Transresveratrol (RESV) has been proved to increase NO and eNOS levels. Thus, RESV could be capable of improving NO dependent vascular relaxation on aortic rings isolated from treated 2K-1C animals through ROS damage reduction. Aim: Evaluate the effects of RESV treatment on the relaxation of aortic rings isolated from treated 2K-1C rats while focusing on the effects of the treatment on systolic blood pressure. Methods: Male Wistar rats (180 g) were grouped: two 2K-1C and two Sham groups, one of each was treated with RESV (20 mg/kg, gavage) dissolved in Tween 80 and one of each was treated with water plus Tween 80 (control) for six weeks. The rats had their systolic blood pressure (SBP) measured before and after the treatments. Vascular reactivity studies were conducted in order to observe and compare acetylcholine (ACh)-induced relaxations in the presence and absence of the NOS inhibitor L-NAME (10-4 mol/L). Results: SBP for 2K-1C was significantly reduced in the treated group (179.13 ± 4.90 mmHg, n = 23) when compared to the untreated group (196.66 ± 6.06 mmHg, n = 15, p < 0.01). The maximum relaxation of aortic rings isolated from the 2K-1C treated group showed a higher efficacy (116.63% ± 1.72%, n = 12) than that from the untreated group (85.97% ± 0.69%, n = 6, p < 0.001);L-NAME exposure was responsible for a significant decrease in each group’s maximum relaxation efficacy. Conclusions: SBP reduction observed after RESV treatment in rat renal hypertension could be due to the reestablishment of vascular relaxation depend of NO.
文摘The binding of Fgn to GPIIb / IIIa has confirmed that there are two distinct amino acid sequences within the Fgn molecule that are responsible for mediating its attachment to GP IIb / IIIa receptor. In addition to monoclonal antibodies, the binding function of GP IIb / IIIa can be blocked by synthetic small peptides containing the RGD and APLRV sequence. In our preliminary study it was found that besides inhibition of platelet aggregation and thrombus formation RGDS showed vasodilation effects as well. In an attempt to confirm the vasodilation effect of RGDS related peptides, RGDF, APLRV, APLRVRGDS and APLRVRGDF were investigated. The effects of these synthetic peptides on rat aortic strips pretreated with NE in vitro were observed. The relaxing extents of contracted strips for the peptides at three doses (10 5 mol / L, 10 6 mol / L and 10 7 mol / L) were recorded.
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Background: Many factors can contribute to atherosclerotic-type vascular changes in older individuals or men. Thus, confining the investigation to young women with no clinical evidence of the condition could enhance understanding of the early stages of cardiovascular disease. The aim of this study was to determine whether carotid mean/max intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) values, which are well-known event-related indices, are associated with laboratory data and the other vascular indices of atherosclerosis in healthy young women. Methods: Carotid mean/max IMT and brachial FMD were measured in young women with no clinical evidence of atherosclerosis (n = 110;mean age, 39 years) who were instructed not to eat, drink or smoke after 9 PM the evening before testing. All participants also underwent laboratory assessment, including simultaneous measurements of arterial stiffness such as augmentation index (AI), cardioankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). Results: Mean IMT was signifi-cantly and positively associated with age (p = 0.002), CAVI (p = 0.044), low-density lipoprotein-cholesterol (LDL-C, p = 0.047) and high-sensitive C-reactive protein (hs-CRP, p = 0.002) values but was not related to FMD, AI, baPWV or triglycerides (TG) in the multivariate regression analysis. Similarly, max IMT was positively associated with age (p p = 0.003) and hs-CRP (p = 0.005) values but was not related to FMD, AI, CAVI, baPWV, TG or blood pressure level in the multivariate regression analysis. The association between LDL-C and max IMT was much stronger than that between LDL-C and mean IMT. Brachial FMD was positively associated only with heart rate in the multivariate regression analysis. Conclusions: These results suggest that mean IMT more closely represents the sclerotic aspect of vascular change, whereas max IMT represents the atherotic aspect in healthy young women. Although the relationship between the autonomic nervous system and heart rate is well-known, there may be a complex interaction between the autonomic nervous system and endothelial function.
文摘A series of new 2 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines and 3 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines have been synthesized. These derivatives were evaluated for inhibitory effects on 85 7 mmol·L 1 K + and 10 4 mmol·L -1 NE (nor epinephrine) induced contraction of rat aorta strips.
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Aim: The aim of this study was to determine the effect of training on endothelium-dependent vasodilatation in patients with coronary artery disease (CAD) after revascularization and healthy young men. Background: Impaired endothelial function has been observed in patients with CAD and those with CAD risk factors. Studies have shown that exercise can enhance endothelial function. Methods: This experimental cross-sectional study was conducted on patients with CAD (3 months after CABG and PCI) and students of medical school in 2011. Endothelium dependent dilation of the brachial artery was determined by using high-resolution vascular ultrasonography through flow-mediated vasodilatation (FMD) after induction of ischemia, and the data were analyzed using SPSS, dependent t-test and ANCOVA. Findings: The findings showed that at baseline, FMD was reduced in revascularized patients, when compared with healthy young men, after 8 weeks, and exercise training significantly improved FMD in patients underwent training group [from 4.31 ± 1.45 (SD)% to 6.15 ± 0.773 (SD)%, p p ed unchanged, and even after aerobic training, it did not significantly modify the brachial artery diameter in these groups. Conclusion: Our study demonstrates that endothelial dysfunction persisting in CAD patients after revascularization and aerobic training can improve endothelial function in different vascular beds in CAD patients and healthy young men. This may contribute to the benefit of regular exercise in preventing and restricting cardiovascular disease.
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.