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At least 937 records · Page 52Linked to original sources

PubMed2004

Effect of fenofibrate on LDL-induced endothelial dysfunction in rats.

Previous investigations have demonstrated that asymmetric dimethylarginine (ADMA) is an important factor contributing to endothelial dysfunction, and that fenofibrate has a protective effect on the endothelium in hyperlipidaemic patients. In the present study in rats treated with native low-density lipoprotein (nLDL), we addressed the question of whether the beneficial effect of fenofibrate on endothelial cells is related to reduction of the ADMA concentration. A single injection of nLDL (4 mg/kg, 48 h) markedly reduced endothelium-dependent relaxation in response to acetylcholine and the plasma level of nitrite/nitrate and increased the plasma concentrations of ADMA, malonyldialdehyde (MDA) and tumour necrosis factor-alpha (TNF-alpha). Treatment with fenofibrate (30 or 100 mg/kg) significantly reduced the inhibition of vasodilator responses to acetylcholine, decreased the elevated levels of ADMA, MDA and TNF-alpha, and enhanced the decreased level of nitrite/nitrate in the rats treated with LDL. These results suggest that the protective effect of fenofibrate on endothelial cells in rats treated with LDL may be related to the reduction of ADMA concentration.

Acetylcholine↗

PubMed2003

Endothelial dysfunction, erectile dysfunction, and coronary heart disease: the pathophysiologic and clinical linkage.

Our rapidly expanding knowledge regarding the biology of the endothelial cell and the pathophysiology of coronary heart disease (CHD) and endothelial dysfunction indicates important common factors and overlapping clinical presentations. We are, in effect, presented with a new paradigm-that of varying vascular manifestations of disease linked to the functioning of endothelial cell lining. This article reviews these areas of advancement and addresses their clinical implications regarding erectile dysfunction and CHD, as well as the role of the phosphodiesterase-5 inhibitor sildenafil.

Journal Article↗

PubMed2000

Temocapril, an angiotensin converting enzyme inhibitor, protects against diabetes-induced endothelial dysfunction.

The effect of chronic treatment with the angiotensin converting enzyme inhibitor, temocapril, on prevention of endothelial dysfunction was evaluated in an experimental model of diabetes mellitus. Endothelium-dependent relaxation to acetylcholine was impaired while endothelium-independent relaxation to nitroglycerin was unaltered in diabetic aortic ring segments. Treatment of diabetic animals with temocapril prevented the impaired endothelium-dependent relaxation without altering responses to nitroglycerin. Acetylcholine-induced relaxation was largely due to nitric oxide (NO)-mediated relaxation; however, a small but significant portion of relaxation in aortic rings from temocapril-treated diabetic rats was resistant to inhibition by the nitric oxide synthase (NOS) inhibitor, L-nitroarginine.

Acetylcholine↗

PubMed2001

Endothelial dysfunction in type 2 diabetes mellitus subjects with peripheral artery disease.

We strived to characterize the endothelial function status in type 2 diabetic patients with peripheral artery disease which was detected by ankle-brachial index by utilizing high frequency ultrasounds. Predictors of endothelial dysfunction were investigated. We chose 23 type 2 diabetic patients had ankle-brachial index <0.97 (0.15-0.95; mean=0.74+/-0.20), 31 diabetic patients had ankle-brachial index >/=1.0 and 28 non-diabetic subjects for study. Older age, a longer duration of diabetes, higher systolic blood pressure, higher prevalence of history of hypertension were observed in patients with peripheral vascular disease. Type 2 diabetic patients showed impaired flow-mediated dilatation than non-diabetic and it showed more impaired in patients with peripheral vascular disease. Nitroglyerin-induced dilatation showed a trend of impairment in patients with peripheral vascular disease but did not reach statistical significance. Age (r=-0.259, P=0.019), baseline brachial artery diameter (r=-0.321, P=0.003), ankle-brachial index (r=0.259, P=0.002) and hypertension history (P=0.01) were significantly associated with flow-mediated dilatation. However, after adjusting for age, only baseline diameter and ankle-brachial index were independent predictors of flow-mediated dilatation. In conclusion, we demonstrated flow-mediated dilatation was impaired in type 2 diabetic patients and it was further impaired in patients with peripheral vascular disease. Nitroglycerin-induced dilatation showed a trend of impairment but did not reach statistical significance.

Aged↗

PubMed2001

Gene transfer of superoxide dismutase isoforms reverses endothelial dysfunction in diabetic rabbit aorta.

Increased production of oxygen free radicals is an important mechanism of endothelial dysfunction in diabetes mellitus. Our goal was to test whether adenovirus (Ad)-mediated gene transfer of copper/zinc (CuZn) or manganese superoxide dismutase (Mn SOD) improves relaxation of diabetic vessels. The aortas from 9 alloxan-induced diabetic mellitus (DM) and 16 control rabbits were used. Control and DM rings were transduced ex vivo with Ad vectors encoding Mn SOD (AdMn SOD), CuZn SOD (AdCuZn SOD), beta-galactosidase (Ad(beta)gal), or diluents. In the absence of gene transfer, SOD activity was significantly increased in DM aortas. Transgene expression in DM AdCuZn SOD and DM AdMn SOD-transduced vessels was confirmed by Western blot analysis and by increased SOD activity (DM AdCuZn SOD, 76.2 +/- 9.3; DM AdMn SOD, 65.2 +/- 4.8; P < 0.05 vs. DM Ad(beta)gal; 50.9 +/- 4.4 U/mg protein). Superoxide production was increased in DM Ad(beta)gal-transduced aorta and relaxations to acetylcholine were impaired in these vessels. Gene transfer of CuZn SOD and Mn SOD corrected both of these defects. Thus Ad-mediated gene transfer CuZn and Mn SOD to the diabetic aorta improves endothelium-dependent relaxation.

Acetylcholine↗

PubMed2005

[Endothelial dysfunction in severe forms of acute renal failure. New approaches to pathogenetic therapy].

AIM: To study endothelial function in different variants of acute renal failure (ARF) at various stages of the disease. MATERIAL AND METHODS: The study of 36 patients with severe ARF at the stages of oliguria and recovery of diuresis included a clinico-laboratory analysis of characteristics of ARF of various etiology and follow-up of plasmic concentrations of endothelin-1, thromboxan A2 and prostacyclin in different ARF variants at different ARF stages. RESULTS: The oliguric phase of severe ARF ran with significant elevation of the level of vasoconstrictive endothelial hormones (endothelin-1 and thromboxan A2 and a fall of a vasodilator prostacyclin. Recovery of diuresis normalized the above parameters. CONCLUSION: Mechanisms of ARF development involve endothelial dysfunction manifesting with alteration of vasoactive hormones synthesis with a dominant rise of a vasoconstrictive hormones concentration.

Acute Kidney Injury↗

PubMed2001

Endothelial dysfunction associated with oxidative stress in human.

The imbalance in pro- and anti-oxidant activity causes endothelial dysfunction, which precedes and exacerbates atherosclerosis. LDL-apheresis improves ischemic symptom in patients with hypercholesterolemia and regresses atherosclerosis. Whereas, patients who undergo hemodialysis experience accelerated atherosclerosis and premature death even though their cholesterol level is known to be normal. We investigated the association between oxidative modification and endothelial function during a single session of blood purification therapies, LDL-apheresis and hemodialysis. To examine the effect of a single session of LDL-apheresis on endothelial function in patients with hypercholesterolemia, we measured forearm blood flow (FBF) by strain gauge plethysmography before and after LDL-apheresis, while infusing acetylcholine (ACh) and sodium nitroprusside (SNP). The single session of LDL-apheresis reduced oxidized-LDL. Although ACh and SNP increased FBF dose-dependently before and after LDL-apheresis, ACh response was significantly augmented without changes in responses to SNP. The plasma level of oxidized LDL correlated with the degree of ACh-induced vasodilatation. To examine the effect of a single session of hemodialysis on endothelial function in patients with end stage renal disease, we estimated flow-mediated vasodilation (FMD) during reactive hyperemia using a high-resolution ultrasonography, before and after a single session of hemodialysis. We also investigated the effect of anti-oxidative modification during hemodialysis using an a-tocopherol acetate-coated or a non-coated cellulose dialyzer. Non-specific endothelium independent vasodilation was measured after sublingual glyceryltrinitrate spray (GTN; 0.3 mg) administration in each session. A single session of hemodialysis increased plasma level of oxidized LDL. Although hemodialysis treatment did not affect GTN-induced vasodilation, a single session of hemodialysis impaired the endothelium-dependent vasodilation. Treatment with vitamin E-coated-dialyzer restored endothelium-dependent vasodilation, which was accompanied by decrease in oxidized LDL. Thus, endothelial function was impaired by acute increase in oxidative stress and was restored by anti-oxidant therapy. Our results suggest the importance of controlling oxidative stress in addition to classical risk factors to preserve human endothelial function.

Arteriosclerosis↗

PubMed1994

Coronary artery endothelial dysfunction after global ischemia, blood cardioplegia, and reperfusion.

This study tests the hypothesis that blood cardioplegia (BCP) attenuates endothelial dysfunction related to nitric oxide after global normothermic ischemia, cardioplegic arrest, and reperfusion in anesthetized open-chest dogs placed on cardiopulmonary bypass. The dogs were divided into five groups to identify the time when endothelial injury occurred: group 1 = control without ischemia; group 2 = 45 minutes of normothermic ischemia only; group 3 = 45 minutes of normothermic ischemia plus unmodified reperfusion; group 4 = 45 minutes of ischemia plus intermittent BCP without reperfusion; and group 5 = ischemia plus BCP and reperfusion. In vitro coronary vascular relaxation responses to the nitric oxide stimulator acetylcholine (endothelium-dependent, receptor-dependent), the calcium ionophore A23187 (endothelium-dependent, receptor-independent), and acidified NaNO2 (endothelium-independent) were measured at the end of the protocol. Maximum in vitro coronary vascular responses to acetylcholine were similar among groups 1, 2, and 4, indicating an absence of endothelial injury. In contrast, significantly impaired relaxations to acetylcholine were demonstrated in the two reperfused groups (groups 3 and 5). Relaxation responses to A23187 and NaNO2 were not altered markedly in any group. Electron microscopy showed intact endothelium in groups 1, 2, and 4. However, moderately severe endothelium damage was seen in groups 3 and 5. We conclude that morphologic and functional endothelial damage occurs after blood reperfusion with or without BCP, and 1-hour hypothermic BCP arrest after normothermic ischemia is not associated with extension of endothelial damage.

Acetylcholine↗

PubMed2002

Endothelial dysfunction in the pathogenesis of atherosclerosis.

A healthy endothelium plays a central role in cardiovascular control. Therefore, endothelial dysfunction (ED), which is characterized by an imbalance between relaxing and contracting factors, procoagulant and anticoagulant substances, and between pro-inflammatory and anti-inflammatory mediators, may play a particularly significant role in the pathogenesis of atherosclerosis. ED is closely related to different risk factors of atherosclerosis, to their intensity and their duration. The involvement of risk factors in ED is also supported by results of intervention studies that showed regression of ED with treatment of risk factors. The common denominator whereby different risk factors cause ED is most probably increased oxidative stress and/or inflammation. ED promotes atherosclerosis and probably plays an important role in the development of thrombotic complications in the late stages of the disease. As ED is a key underlying factor in the atherosclerotic process, markers of endothelial abnormalities have been sought. Detection of ED is based on tests of endothelium-dependent vasomotion (dilation capability of peripheral and coronary arteries) and on circulating markers of endothelial function (endothelin-1, von Willebrand factor, tissue plasminogen activator, plasminogen activator inhibitor, adhesion molecules). Using these tests it is possible to follow the dose-response of harmful effects or risk factors, and the effects of preventive procedures on vessel wall function.

Arteriosclerosis↗

PubMed2004

Inflammation and endothelial dysfunction: intimate companions in the pathogenesis of vascular disease?

There is increasing evidence to implicate inflammation as an important precursor of endothelial dysfunction. This mechanistic link is apparent across the entire spectrum of inflammatory status, i.e. endothelial function is apparent following acute infection, and in subjects with chronic high-grade inflammation and, perhaps most importantly, persistent low-grade inflammation. The recognition of this relationship has present therapeutic ramifications, but also requires that future longitudinal studies determining the predictive ability of endothelial function measures for vascular events should incorporate markers of inflammation as potential confounders. In this issue of Clinical Science, Fichtlscherer and co-workers describe a link between endothelial function and sPLA(2) (secretory non-pancreatic type II phospholipase A(2)) serum activity.

C-Reactive Protein↗

PubMed2001

Study of the reversibility of endothelial dysfunction in a rat model of diabetes mellitus: experimental treatment by transplantation of pancreatic islets.

OBJECTIVE: To study the endothelial dysfunction induced in a rat model of diabetes mellitus, and to find out if transplantation of islet cells is an effective treatment for the endothelial damage. DESIGN: Experimental study. SETTING: University hospital, Spain. ANIMALS: 24 Wistar rats in 3 groups of each: control, diabetic and transplanted. INTERVENTIONS: Diabetes was induced in the diabetic and transplanted animals by intravenous injection of streptozocin 45 mg/Kg. In the transplanted group fresh pancreatic islet from syngeneic donor rats (1200-1500/receptor) were injected intraportally 16 weeks after the induction of diabetes. The rats were killed at 18 weeks. Excision of rings of thoracic aorta, which were contracted with 0(-5) M phenylephrine. Once the maximum contraction had been reached relaxation was induced with 10(-5) M acetylcholine and then 10(-4) M independent nitroprusside endothelial vasodilator was added. MAIN OUTCOME MEASURES: Blood glucose concentrations throughout the experiment. Mean vasodilator response to acetylcholine as an indicator of recovery of endothelial function. RESULTS: The mean (SD) vasodilatation in the control group differed significantly from that in the diabetic group (27.6 (3.9) g compared with 20.1 (3.9) p = 0.002). The transplanted group also differed from the diabetic group (25.8 (3.6) g, p = 0.009). There was no significant difference between the transplanted group and the control group (p = 0.33). CONCLUSION: In rats diabetes mellitus causes considerable endothelial damage, which can be reversed by transplantation of pancreatic islets.

Acetylcholine↗

PubMedDate not supplied

The ambulatory monitoring documents a more elevated blood pressure regimen (pre-hypertension) in normotensives with endothelial dysfunction.

PURPOSE: The present study investigates the blood pressure (BP) 24-h values in normotensives with and without endothelial dysfunction (ED). The scope is to detect differences in BP regimen supporting the hypothesis that the ED is associated with vasopressant effects that can cause a condition of "pre-hypertension". MATERIALS AND METHODS: Thirty-eight normotensives were investigated in their endothelial function by mean of the non-invasive post-ischemic brachial artery vasodilation test (endothelium-dependent vasomotricity). Their were also automatically and non-invasively monitored in their systolic (S) and diastolic (D) BP over the 24-h period in order to confirm that they were not hypertensive. RESULTS: Eight of the investigated normotensives were found to show an ED. A significantly higher daily mean level as well as a more prominent nychtohemeral variability in SBP and DBP 24-h values were observed in the normotensives with ED as compared to the normotensives without ED. The higher BP regimen in the normotensives with ED was found to maintain a circadian rhythm. However, a significant amplification the second harmonic component, with a 12-h period, was observed. The different structure of the BP 24-h pattern in the normotensives with ED was confirmed by the detection of additional ultradian components at the linear-in-period spectral analysis. CONCLUSIONS: The present study documented a significant elevation of BP 24-h values in normotensives with ED that is the reflex of consistent changes in the frequency organization of the BP circadian pattern. The elevation of BP regimen suggests that the ED is associated with vasopressant effects even in normotensives. Such a condition of higher BP in normotensives with ED can be regarded as a status of "pre-hypertension".

Adult↗

PubMed2006

Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats.

BACKGROUND AND OBJECTIVE: Several studies have found that chronic treatment with the dietary flavonoid quercetin lowers blood pressure and restores endothelial dysfunction in hypertensive animal models. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein expression and activity, and reduced reactive oxygen species might be involved in the improvement of endothelial function induced by quercetin in spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male SHR and Wistar-Kyoto (WKY) rats (5 weeks old) were treated with quercetin (10 mg/kg) or vehicle for 13 weeks. Changes in vascular expression of eNOS, caveolin-1 and p47 were analysed by Western blot, eNOS activity by conversion of [H]arginine to L-[H]citrulline, and NADPH oxidase activity by NADPH-enhanced chemoluminescence of lucigenin. RESULTS: In SHR, quercetin reduced the increase in blood pressure and heart rate and enhanced the endothelium-dependent aortic vasodilation induced by acetylcholine, but had no effect on the endothelium-independent response induced by nitroprusside. However, quercetin had no effect on endothelium-dependent vasoconstriction and aortic thromboxane B2 production. Compared to WKY, SHR showed upregulated eNOS and p47 protein expression, downregulated caveolin-1 expression, increased NADPH-induced superoxide production but, paradoxically, eNOS activity was reduced. Chronic quercetin treatment prevented all these changes in SHR. In WKY, quercetin had no effect on blood pressure, endothelial function or the expression or activity of the proteins analysed. CONCLUSIONS: Enhanced eNOS activity and decreased NADPH oxidase-mediated superoxide anion (O2) generation associated with reduced p47 expression appear to be essential mechanisms for the improvement of endothelial function and the antihypertensive effects of chronic quercetin.

Acetylcholine↗

PubMed2000

Endothelial dysfunction in men with small LDL particles.

BACKGROUND: It is unknown whether LDL particle size is, independent of other lipids and lipoproteins, associated with endothelial dysfunction in vivo. METHODS AND RESULTS: We determined in vivo endothelial function in 34 healthy men by measuring forearm blood flow responses to intrabrachial artery infusions of acetylcholine (ACh, an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator). LDL peak particle size was measured with gradient gel electrophoresis. Men with small LDL particles (LDL diameter </=25.5 nm, n=10) had a 39% lower blood flow response to ACh than men with large LDL particles (LDL diameter >25. 5 nm, n=24, blood flow 6.9+/-3.6 versus 11.4+/-5.1 mL/dL. min, P=0. 006). The groups had comparable LDL cholesterol concentrations (3. 9+/-0.6 versus 3.7+/-1.0 mmol/L, men with small versus large LDL particles), blood pressure, glucose concentrations, and body mass indexes. LDL size (r=0.45, P=0.01) but not HDL cholesterol (r=0.31, P=0.09) or triglycerides (r=-0.19, P=0.30) was significantly correlated with endothelium-dependent vasodilation. Serum triglyceride concentrations and LDL size were inversely correlated (r=-0.44, P=0.01). In multivariate regression analysis, LDL size was the only significant determinant of the ACh-induced increase in blood flow. Sodium nitroprusside-stimulated endothelium-independent vasodilation was similar in both groups. CONCLUSIONS: Small LDL particles are associated with impaired in vivo endothelial function independent of HDL and LDL cholesterol and triglyceride concentrations. LDL size may therefore mediate adverse effects of hypertriglyceridemia on vascular function.

Acetylcholine↗

PubMed2004

The procyanidin-induced pseudo laminar shear stress response: a new concept for the reversal of endothelial dysfunction.

Reduced endothelium-dependent vasodilator responses with increased synthesis of ET-1 (endothelin-1) are characteristics of endothelial dysfunction in heart failure and are predictive of mortality. Identification of treatments that correct these abnormalities may have particular benefit for patients who become refractory to current regimens. Hawthorn preparations have a long history in the treatment of heart failure. Therefore we tested their inhibitory effects on ET-1 synthesis by cultured endothelial cells. These actions were compared with that of GSE (grape seed extract), as the vasoactive components of both these herbal remedies are mainly oligomeric flavan-3-ols called procyanidins. This showed extracts of hawthorn and grape seed were equipotent as inhibitors of ET-1 synthesis. GSE also produced a potent endothelium-dependent vasodilator response on preparations of isolated aorta. Suppression of ET-1 synthesis at the same time as induction of endothelium-dependent vasodilation is a similar response to that triggered by laminar shear stress. Based on these results and previous findings, we hypothesize that through their pharmacological properties procyanidins stimulate a pseudo laminar shear stress response in endothelial cells, which helps restore endothelial function and underlies the benefit from treatment with hawthorn extract in heart failure.

Animals↗

PubMed1998

Endothelium-dependent vasodilatation in Sprague-Dawley rats with postinfarction hypertrophy: lack of endothelial dysfunction in vitro.

The hypothesis was tested whether postinfarction hypertrophy/congestive heart failure in rats is associated with endothelial dysfunction and increased vascular generation of reduced oxygen species. Myocardial infarction was induced in Sprague-Dawley rats by ligation of the left coronary artery. After 16 weeks, endothelium-dependent (with acetylcholine) and -independent (with sodium nitro-prusside) relaxations were studied in isolated aortic rings, and isolated rings from the femoral and mesenteric arteries. The generation of superoxide, hydrogenperoxide, and peroxynitrite was measured in arteries using lucigenin- and luminol-enhanced chemiluminescence techniques. Systolic blood pressure decreased over the 16 week study period as compared to shamoperated control rats; organ weights (lungs, right and left ventricles) significantly increased in coronary artery ligated rats indicating development of congestive heart failure. Surprisingly, concentration response curves with acetylcholine and sodium nitroprusside were almost identical in myocardial infarction rats as compared to control animals, irrespective of which type of vessel was studied (aorta, femoral or mesenteric arteries). In addition, no differences in the production of reduced radical species were found in aortic tissue from heart failure rats as compared to control rats.

Acetylcholine↗

PubMed2002

Detection of endothelial dysfunction in preeclamptic patients by using color Doppler sonography.

Our goal in this study was to detect endothelial function in normal and preeclamptic patients by using color Doppler sonography and plasma fibronectin levels. The increased ratio of the brachial artery diameter during shear stress, and plasma fibronectin levels were measured in 15 preeclamptic and 11 normal, gestational-age matched pregnant patients. The test was repeated at the postpartum second and sixth weeks in the preeclamptic group. In addition, the plasma fibronectin levels of all patients were measured. The increased ratios were 4.26+/-0.69% vs 12.18+/-1.97% in the preeclamptic and normal patients, respectively ( P=0.003). At the second and sixth postpartum weeks, the ratios were 6.67+/-0.89% and 9.27+/-1.16% in the preeclamptic group, revealing a significant improvement in the sixth week ( P=0.001). Fibronectin levels were 0.80+/-0.11 g/L vs 0.45+/-0.06 g/L in preeclamptic and normal patients ( P=0.01). The correlation coefficient between the fibronectin levels and increase rate was r=-0.38 and P=0.05. We conclude that endothelial dysfunction, which is fundamental to preeclampsia, can be detected by using color Doppler sonography.

Adult↗

PubMed2000

Autonomic and endothelial dysfunction in experimental diabetes.

The effect of streptozotocin induced diabetes on autonomic regulation of heart rate and endothelial function was examined in Sprague-Dawley rats. Weanling rats (3-4 weeks of age) of either sex were randomly assigned to a non-diabetic (male 5, female 6) or diabetic (male 4, female 5). Diabetes was induced with a single intraperitoneal (IP) injection of streptozotocin (STZ, 100 mg/kg). Nondiabetic rats received an IP injection of saline. Eight weeks after injection, rats were chronically instrumented with a left jugular venous catheter and a left carotid arterial catheter. After recovery (5 days) cardiac sympathetic tonus, parasympathetic tonus and intrinsic heart rate were determined. On an alternative day, the pressor response to nitric oxide synthase inhibition (NOS-X) was determined in areflexic rats. Cardiac sympathetic tonus (72 +/- 13 vs. 41 +/- 7), parasympathetic tonus (-51 +/- 10 vs. -22 +/- 7), and intrinsic heart rate (368 +/- 6 vs. 292 +/- 9), were reduced in diabetic rats. Furthermore, diabetic rats had a smaller pressor response (A33 +/- 7 vs. A66 +/- 5) to NOS-X. These results document impaired autonomic control of heart rate and endothelial dysfunction in 8-week streptozotocin induced diabetic rats.

Adrenergic beta-Antagonists↗