Axonotmesis-evoked plantar vasodilatation as a novel assessment of C-fiber afferent function after sciatic nerve injury in rats

Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.

Combined antihypertensive effect of GSY and metoprolol,based on endothelium-dependent vasodilatation function

OBJECTIVE To investigate the synergistic effect on dilating blood vessels and anti-hypertension of GYS combined with metoprolol.METHODS ① Spontaneously hypertensive rats(SHR)were administered orally with the vehicle,GSY,metoprolol or GSY combined with metoprolol for 4weeks.Blood pressure,which included SBP,DBP and MBP was measured by a noninvasive method every week.At the end of4 weeks,blood was drawn from the ophthalmic venous plexus to determine blood fat levels(serum TC,TG,LDL-c,HDL-c),liver function(serum ALT,AST),and kidney function(serum BUN,UA and Cr)by the ACCUTE(TBA-40FR)automatic.② The aortae of normal SD rats were prepared and cleaned from periadventitial fat and surrounding connective tissue and cut transversely into 4-mm width rings.To observe different concentration of GYS,metoprolol or GSY combined with metoprolol causing relaxation of the isolated aortic rings precontracted until a stable plateau by noradrenaline(NA)directly or in the presence of eNOS inhibitor L-NAME and cyclooxygenase inhibitor indomethacin(INDO)respectively.③ The concentrations of plasma GSY was determined by the HPLC after rats administered orally with GSY or GSY combined with metoprolol for single-dose.DAS data processing software calculated the pharmacokinetic parameters of GSY.RESULTS There was a significant synergism between GYS and metoprolol in lowering blood pressure and the concentrations of serum TC and LDL-c of SHR.The relaxant effect of GYS combined with metoprolol on the aortic rings precontracted by NA could be attenuated by L-NAME or INDO.The AUC0-tof GSY significantly increased after in conjunction with metoprolol.CONCLUSION GYS combined with metoprolol increases the concentrations of plasma GSY and synergistically lowers blood pressure based on endothelium-dependent vasodilatation function(EDVF).

mpaired flow-mediated vasodilatation in Asian Indians with erectile dysfunction

Endothelial dysfunction is the postulated link between coronary artery disease （CAD） and erectile dysfunction （ED）. Brachial artery flow-mediated vasodilatation （FMD） is a non-invasive surrogate marker for endothelial function assessment. Despite Asian Indians representing a considerable global CAD burden, data on FMD and ED in these patients are lacking. Of the 225 patients undergoing coronary angiography, 72% had ED （assessed using the International Index of Erectile Function （IIEF-5） questionnaire）; ED was moderate to severe in 61% of the patients. ED patients had a higher incidence of severe and diffuse angiographic CAD, a greater number of coronary vessels involved and a lower mean brachial artery FMD （6.40%±4.60% vs. 9.10%±4.87%, P〈0.001） compared to non-ED patients. A progressive reduction in FMD was noted with increasing severity of ED. Impaired FMD （ ≤ 5.5%） was twice as common in ED patients （52% vs. 24% without ED）. Patients with impaired FMD had higher ED prevalence （85% vs. 62%） and lower mean I IEF-5 scores compared to those with normal FMD. Impaired FMD was a significant ED predictor independent of other risk factors （odds ratio, 2.33; 95% confidence interval： 0.59-9.23; P=0.03）. An inverse correlation between FMD and ED severity was observed （r=-0.22; P=0.004）. ED is common among Asian Indians with angiographically documented CAD. Patients with ED have impaired FMD independent of other risk factors, suggesting that endothelial dysfunction is the underlying pathophysiology. Urologists and cardiologists need to be aware of the association between ED, CAD and endothelial dysfunction.

The effect of aerobic training on endothelium-dependent vasodilatation in patients with coronary artery disease who were revascularized and young men

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.

The relation of flow-mediated vasodilatation and diastolic function in uncomplicated Type 2 diabetic patients

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.

Chilean crude extract of <i>Ruta graveolens</i>generates vasodilatation in rat aorta at subtoxic cellular concentrations

In Chile elevated percentage of population have cardiovascular diseases, 70% of this populations is a hypertensive peoples. The Ruta graveolens (Ruta) is a medicinal plant used in different parts of the world with different therapeutics properties like dermatologic as far as anti-helmintic properties. We analyzed the vascular action measuring the tension to identify vasodilator effect of Ruta extract in norm-tense rat’s aorta incubated and measured in isolated organ bath, and evaluating the toxicity effect in CRL-1730 cell line, through enzymatic assay (MTT), confocal microscopy (propidium iodide stain) and flow cytometry (TUNEL assay), including extracellular reactive oxygen species (ROS) production through luminescence assay. The results show with DE50 29 ± 0.1 μg/mL evidenced vasodilatation, partially endothelium-depend. The cytotoxicity showed with DE50 304.6 ± 2 μg/mL in enzymatic assay (MTT) while evidenced membrane permeability in high concentrations (1500 μg/mL), DNA fragmentation in absence of oxidative stress in only observed when high concentrations of Ruta are used over the cell culture. The vasodilatation activity is executed in subtoxic concentration and partially endothelium-depend without permeability effect in the membrane and deterioration of the cells viability suggesting a complex effect of Ruta preparation in the regulation of vascular tone.

Paeonol Induces Vasodilatation in Rat Mesenteric Artery via Inhibiting Extracellular Ca^(2+) Influx and Intracellular Ca^(2+) Release

To investigate the vasodilative effect of paeonol in rat mesenteric artery and the mechanisms responsible for it. Methods： Rats were anaesthetized and sacrificed. The superior mesenteric artery was removed, dissected free of adherent tissue and cut into 2.0 mm long cylindrical segments. Isometric tension of artery rings was recorded by a myograph system in vitro. Concentration-relaxation curves of paeonol （17.8 μmol/L to 3.16 mmol/L） were recorded on artery rings precontracted by potassium chloride （KCI） and concentration-contraction curves of KCI, 5-hydroxytryptamine （5-HT）, noradrenaline （NA） or calcium chloride （CaCI2） were recorded in the presence of paeonol （10^-4.5, 10^-3.8, 10^-3.5 tool/L） respectively. And also, concentration- relaxation curves of paeonol were recorded in the presence of different potassium channel inhibitors and propranolol on rings precontracted with KCI respectively. To investigate the role of intracellular Ca2. release from Ca2. store, the contraction induced by NA （100μmol/L） and CaCI2 （2 mmol/L） in Ca^2＋ free medium was observed in the presence of paeonol respectively. Results： Paeonol relaxed artery rings precontracted by KCI in a concentration-dependent manner and the vasodilatation effect was not affected by endothelium denudation. Paeonol significant decreased the maximum contractions （Emax） induced by KCI, CaCl2, NA and 5-HT, as well as Emax induced by NA and CaCI2 in Ca^2＋-free medium, suggesting that paeonol dilated the artery via inhibiting the extracellular Ca2. influx mediated by voltage-dependent calcium channel, and receptor-mediated Ca^2＋-influx and release. Moreover, none of glibenclamide, tetraethylammonium, barium chlorded and propranolol affected the paeonol-induced vasodilatation, indicating that the vasodilatation was not contributed to ATP sensitive potassium channel, calcium-activated potassium channel, inwardly rectifying potassium channel, and β-adrenoceptor. Conclusion： Paeonol induces non-endothelium dependent-vasodilatation in rat mesenteric artery via inhibiting voltage-dependent calcium channel-mediated extracellular Ca^2＋ influx and receptor-mediated Ca^2＋ influx and release.

Cirrhotic portal hypertension: From pathophysiology to novel therapeutics

Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pathogenesis of portal hypertension and attempts to provide an update on currently available therapeutic approaches in the management of portal hypertension with special emphasis on how the alternate RAS could be manipulated in our search for development of safe, specific and effective novel therapies to treat portal hypertension in cirrhosis.

Overproduction of nitric oxide inhibits vascular reactivity in portal hypertensive rats

IM To evaluate the relationship between nitric oxide (NO) and hyperdynamic circulatory status in portal hypertension.METHODS Twenty male SpragueDawley rats (weighing 200g±20g) randomized into two groups, portal hypertension group (n=12) and the controls (n=8). Portal hypertensive models were established by means of graded constriction of the portal vein. The concentrations of nitrite (NO2) in portal vein and peripheral blood were measured to reflect NO levels with flourimetric analysis. The reactivitiy of isolated abdominal aortic rings from partial portal veinconstricted and shamoperated rats was observed by potassium chloride (KCl) (10mmol/L-80mmol/L) and phenylephrine (10-9mol/L10-4mol/L) with or without NO synthase inhibitor NωnitroLarginine (LNNA).RESULTS Serum concentrations of NO2 in portal vein (0766μmol/L±0097μmol/L) and peripheral blood (0687μmol/L±0092μmol/L) were elevated in portal hypertensive rats as compared with those in controls (0613μmol/L±0084μmol/L, 0591μmol/L±0045μmol/L, P<001, respectively). The rates of NO2 in portal vein blood were markedly higher than those in peripheral blood (P<005) of portal hypertensive rats. Abdominal aortic rings from portal veinconstricted rats exhibited significantly impaired contractility to phenylephrine and potassium chloride as compared with the controls. The EC50 values of KCl were markedly higher in portal hypertensive rings (265mmol/L±09mmol/L) than those of the control rings (223mmol/L±17mmol/L, P<001), and so were the EC50 values of phenylephrine (372nmol/L±04nmol/L) vs (281nmol/L±02nmol/L, P<001). After preincubation of rings with LNNA, the difference in EC50 values no longer statistically significant between portal hypertensive and control rings in both KCl (2018mmol/L±08mmol/L, and 194mmol/L±12mmol/L, P>005) and phenylephrine (224nmol/L±18nmol/L, 218nmol/L±14nmol/L, P>005). However, the maximal KCl and phenylephrineinduced contractions were still lower in portal hypertensive rings (KCl: 108g±01g, phenylephrine: 143g±014g) than those of the control rings (KCl: 121g±011g, phenylephrine: 172g±011g, P<005, respectively). This showed that addition of the NO synthase inhibitor LNNA could partially restore contractile responses to KCl and phenylephrine in portal hypertensive rings.CONCLUSION NO overproduction inhibits the vascular reactivity to vasocontrictors, and it might be one of the main causes which results in vasodilatation and hyperdynamic circulatory status in portal hypertension.

Plants Used as Antihypertensive

Hypertension is a critical health problem and worse other cardiovascular diseases.It is mainly of two types:Primary or essential hypertension and Secondary hypertension.Hypertension is the primary possibility feature for coronary heart disease,stroke and renal vascular disease.Herbal medicines have been used for millions of years for the management and treatment of hypertension with minimum side effects.Over aim to write this review is to collect information on the anti-hypertensive effects of natural herbs in animal studies and human involvement as well as to recapitulate the underlying mechanisms,from the bottom of cell culture and ex-vivo tissue data.According to WHO,natural herbs/shrubs are widely used in increasing order to treat almost all the ailments of the human body.Plants are the regular industrial units for the invention of chemical constituents,they used as immunity booster to enhance the natural capacity of the body to fight against different health prob-lems as well as herbal medicines and food products also.Eighty percent population of the world(around 5.6 billion people)consume medicines from natural plants for major health concerns.This review provides a bird’s eye analysis primarily on the traditional utilization,phytochemical constituents and pharmacological values of medicinal herbs used to normalize hypertension i.e.Hibiscus sabdariffa,Allium sativum,Andrographis paniculata,Apium graveolens,Bidenspilosa,Camel-lia sinensis,Coptis chinensis,Coriandrum sativum,Crataegus spp.,Crocus sativus,Cymbopogon citrates,Nigella sativa,Panax ginseng,Salviaemiltiorrhizae,Zingiber officinale,Tribulus terrestris,Rauwolfiaserpentina,Terminalia arjuna etc.

Pharmacological characteristics of Kampo medicine as a mixture of constituents and ingredients

Herbal medicine in Japan is termed as Kampo medicine, which is derived from traditional Chinese medicine. Shakuyakukanzoto （Shao-Yao-Gan-Cao-Tang） as a kind of Kampo formulations is composed of just two components; Paeoniae Radix and Glycyrrhizae Radix, which produced marked relaxation of intestinal tract. Mokuboito （Mu-Fang-Ji-Tang） inhibited cardiac ionic channel currents, and as a mixture also produced great vasodilatation. Sinomenine （a main ingredient of Mokuboito） as a single compound also caused the vasodilatation, but decreased it along with ageing. Gypsum containing in Mokuboito and Chotosan （Diao-Teng-San） caused more marked effects, as compared with those without Gypsum. On the other hand, Rokumigan （Liu-Wei-Wan）, Hachimijiogan （Ba-Wei-Di-Huang-Wan） and Goshajinkigan （Niu- Che-Shen-Qi-Wan） increase in order the number of contained ingredients. The formulations with more herbs （ingredients） produced much more effective actions on rat aorta, presumably due to compensation of the decline of pharmacological sensitivity with ageing. Thus, there are some important differences between single chemical drugs and mixture drugs with many ingredients. The effects of Kampo medicine （mixture） are never just a sum of each effect induced by a lot of in qredients. For elder persons, furthermore, Kampo medicine exerts more effective actions.

Therapeutic potential of targeting the renin angiotensin system in portal hypertension

Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis.Drug therapy to reduce portal pressure involves targeting two vascular beds.The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells.The second approach is to reduce mesenteric and portal blood flow.Non-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis.However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients.Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding.This review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this condition.It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered "alternate axis" of the RAS.

Liver cirrhosis and arterial hypertension

Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems （renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin）, and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin generelated peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective （although relative） counterbalance to increased arterial blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension （essential, secondary） may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most likely includes the combination of vasodilatation and vasoconstriction in parallel.

Hepatopulmonary syndrome: An update

Hepatopulmonary syndrome(HPS)is characterized by defects in oxygenation caused by intra-pulmonary vasodilation occurring because of chronic liver disease,portal hypertension,or congenital portosystemic shunts.Clinical implications of portal hypertension are very well-known,however,awareness of its effect on multiple organs such as the lungs are less known.The presence of HPS in chronic liver disease is associated with increased mortality.Medical therapies available for HPS have not been proven effective and definitive treatment for HPS is mainly liver transplantation(LT).LT improves mortality for patients with HPS drastically.This article provides a review on the definition,clinical presentation,diagnosis,and management of HPS.

Analysis of the Effects of Botulinum Toxin Type A to Promote the Survival of Transverse Rectus Abdominis Myocutaneous Flaps in an Animal Model

The transverse rectus abdominis myocutaneous (TRAM) flap is one of the techniques for breast reconstruction surgery and other defects. Assuring the vascular input is the main factor that it should be ensured for the survival of the fap. Objective: The article presented is an experimental study, with the objective of evaluating the effect of the vasculature on the myocutaneous flaps of the abdominal rectum with botulinum toxin type A (TBoA) thay may improve the survival of the tissue by promoting the blood perfusion in distal parts of the flap and diminish the risk of necrosis. Material and methods: A total of 30 Wistar male rats, dissect pedicled right TRAM flap in all rats, divided into three groups: Group 1 was applied in saline solution 0.9%;Group 2 was applied in pre surgically TBoA (1 week before lifting the flap);Group 3, will apply TBOA Trans surgical. Results: Histological analysis showed: increased vascularity in group 2 TBoA compared with the saline solution with P < 0.05 statistically significant. In terms of fibrosis, inflammation and granulation tissue, there was no statistically significant difference at p = 0.6. Muscle atrophy was higher in the group of TBoA in the saline group p < 0.05. It was concluded that botulinum toxin type A prevents vasoconstriction of the vessel and promotes vasodilation subsequently lifting the muscle flap, no complications were observed in the groups with TBoA so it can be considered a safe substace and can be used for further studies.

Can Sitaglipten Attenuate Hypertension, Myocardial Changes and Vascular Reactivity Induced by Long Term Blockade of Nitric Oxide Synthesis in the Rat?

Background: Glucagon-like peptide-1 (GLP-1) is an incretin hormone with insulinotropic properties that regulates glucose metabolism. GLP-1 receptors are the most extensively key modulators of lipid and glucose homeostasis. They are predominantly expressed in adipose tissues, some non adipose tissues including heart, kidney, spleen, and all relevant cells of the vasculature: endothelial cells, smooth muscle cells, and macrophages. The vascular distribution suggests their involvement in the control of cardiovascular function. Objective: The present experiment was designed to study the effect of sitaglipten alone or in combination with captopril on blood pressure, antioxidant enzymes, vascular reactivity and cardiac hypertrophy in NG-nitro-L-arginine methylester (L-NAME) induced hypertension in rats. Methods: One hundred male albino rats weighing from 150 - 200 g were included in this study. Rats were divided into two main groups. Group I, (20 rats) served as a control group for group II, and received 1 ml of physiological saline (0.9%), orally for seven weeks. Group II: hypertensive group, (80 rats) was given daily L-NAME in a dose of 40 mg/kg orally for seven weeks. Rats were further subdivided into A, B, C, and D, each of 20 rats. Group-A, received 1 ml of distilled water daily orally for six weeks, starting one week after L-NAME administration. Groups B, C and D were treated with daily sitaglipten (10 mg/kg b.wt. orally) and captopril (100 mg/kg b.wt. orally), alone or together for six weeks. Blood pressure, serum tumor necrosis factor-α (TNF-α), body weight (BW) and heart weight (HW) were measured. Malondialdehyde (MDA) and reduced glutathione (GSH) were estimated in cardiac tissues. Thoracic aorta was isolated and the aortic rings were allowed to achieve maximal tension by cumulative addition of phenylephrine (PE) (10-9-10-5 M) to the bath solution. Results: Sitaglipten and captopril, alone or together produced significant decreases in blood pressure and TNF-α. Higher oxidative stress accompanying hypertension was significantly reduced by sitaglipten and captopril treatment. The results showed that both drugs significantly attenuated the augmented contractile response to PE in hypertensive rats. In addition, they inhibited the cardiac hypertrophy (reduction in HW/BW ratio). Conclusion: These data suggest that DPP4 inhibitor (sitaglipten) “is away from being insulinotropic and regulates glucose metabolism”, contributes to normal regulation of blood pressure and exerts protective effects in hypertension via many mechanisms, as inhibition of generation of free radicals.

Effects of Scopolamine on Blood Vessels in Rabbit Ear after Sympathetic and Sensory Denervation

Objectives To investigatethe effects and involved mechanisms of scopolamine(Scop) on rabbit ear blood vessels. Methods Rabbitear blood vessels were desympathetic and desensoryinnervation with surgical operation. Diameters of dor-sal auricular arterial trunks in vivo were measuredwith a pair of compasses and the ruler in a dissectingmicroscope, and effluents from isolated ear underconstant perfusion pressure were recorded with a digi-tal drop-recorder. Results Intramuscular injectionof Scop 0.1 mg/kg made the diameter of denerveddorsal auricular arterial trunks, as well as that of in-nerved ones, significantly increased. Scop by itself,atthe maximal concentration (Cmax) of 3μM, 30μMand 300μM, did not alter the effluent flow from theisolated denervated rabbit ear, but chlorpromazine(CPZ), at Cmax of 1μM, acetylcholine (ACh), 0.25μM, all significantly increased the effluent flow, andnorepinephrine (NE), 0.1μM, significantly decreasedthe effluent. Scop, 3μM, did not affect ACh (0.25μM)-induced the increase of effluent flow, but Scop,30μM, alleviated the increase. Scop, 3μM, did notaffect NE (0.1μM)-induced the decrease of effluentflow, but Scop, 10, 30 and 100μM, significantly alle-viated the decrease. Conclusions The study sug-gests that Scop has no direct vasodilator effect. Thevasodilator effect of Scop is not due to the blockade ofmuscarinic receptor. However, Scop can dilate bloodvessels contracted by α_1-adrenoceptor activation.

Pitavastatin calcium improves endothelial function and delays the progress of atherosclerosis in patients with hypercholesterolemia

Background： Statins have proven efficacy in inhibiting the onset and progress of atherosclerosis. The effectiveness of pitavastatin in reversing carotid atherosclerosis associated with hypercholesterolemia （HC） is un-known. Objectives： To explore the simultaneous effects of pitavastatin calcium on brachial arterial flow-mediated vasodilatation （FMD）, carotid intima-media thickness （IMT）, and arterial stiffness （β）, three surrogate markers of ath-erosclerosis were studied in HC patients. Methods：A randomized, double-blind trial was performed with 40 HC sub-jects who fulfil ed the inclusion/exclusion criteria. Patients were given pitavastatin calcium 1 mg/d （Group 1） or 2 mg/d （Group 2） for 8 weeks. There were 20 patients in each group, and 30 gender-and age-matched healthy subjects as controls were recruited. FMD of the brachial artery, carotid IMT, and arterial stiffness indicated byβwere measured at baseline and at 8 weeks after starting pitavastatin calcium therapy using ultrasound techniques. Biochemical tests were also made on al subjects. Results： At baseline, higher total cholesterol （TC） and low-density lipoprotein cho-lesterol （LDL-C）, reduced FMD, and increasedβand IMT were observed in HC patients （P0.05）. Significant negative interactions between TC/LDL and FMD （P〈0.05–0.001）, positive interactions between TC and IMT （P=0.003） and between TC/LDL and β （P〈0.001–0.000） were found. Conclusions： Treatment with pitavastatin calcium exerted fa-vorable effects on endothelial function and arterial stiffness. It also improved carotid atherosclerosis in patients with HC.

Effect of micronized fenofibrate on vascular endothelial function in patients with hypertriglyceridemia

Objective To investigate the effect of micronized fenofibrate on vascular endothelial function in patients with hypertriglyceridemia.Methods Using high-resolution ultrasound, we measured flow- and nitroglycerin-induced dilatation of the brachial artery in 30 patients with hypertriglyceridemia before and after treatment with micronized fenofibrate at a dose of 200 mg once daily for 4 weeks. Simultaneously, both serum lipid and plasma endothelin (ET) levels were determined.Results After micronized fenofibrate therapy, serum triglyceride (TG) levels decreased significantly (P<0. 05). Plasma ET levels also decreased markedly [(82.66 ±15.46) μg/L vs. (106.22 ±19.16) Mμg/L, P< 0.001]. Flow-induced vasodilatation was much improved (11.0% ±9.0% vs 2. 7%±2. 0% , P<0. 01). However, no significant changes in vasodilatation occurred in response to nitroglycerin (16. 2% ±6. 0% vs 15. 0% ±5. 0% , P>0. 05) in patients with hypertriglyceridemia.Conclusions Micronized fenofibrate can improve impaired endothelium-dependent vasodilatation in patients with hypertriglyceridemia. Improving endothelial function may also be the mechanism responsible for the beneficial effects of micronized fenofibrate.