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Results for “Endothelial function”

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PubMed2004

Endothelial function in post-menopausal women: effect of folic acid supplementation.

BACKGROUND: Higher than normal homocysteine levels are associated with an increased incidence of adverse cardiovascular events in post-menopausal women, perhaps via hyperhomocysteinaemia-induced vascular endothelial damage. Because folic acid supplementation reduces homocysteine levels, we attempted to evaluate whether folic acid supplementation may affect endothelial function in post-menopausal women. METHODS: Brachial artery flow-mediated dilatation (endothelium-dependent) and nitroglycerin-induced dilatation (endothelium-independent) before and after a methionine load were analysed in 15 healthy post-menopausal women. Plasma levels of folate, homocysteine, glucose, insulin and lipids were measured, as was blood pressure. All studies were repeated after 1 month supplementation with 7.5 mg/day of folic acid. RESULTS: After folate, endothelial function rose 37% over pre-folic acid supplementation value (P < 0.001), and flow-mediated dilation before folic acid was reduced by 62% subsequent to methionine loading (P < 0.0001); this reduction was still present after folic acid, but was only 19% (P < 0.001). Nitroglycerin-induced dilatation did not change in response to methionine loading before or after folic acid supplementation. Among the other cardiovascular risk factors studied, only high-density lipoprotein (HDL)-cholesterol and low-density lipoprotein (LDL)-cholesterol showed significant changes after folic acid supplementation, with a 6% increase (P < 0.03) and a 9% decrease (P < 0.03) respectively. CONCLUSIONS: Although preliminary, these results indicate that folic acid supplementation may improve endothelial function and lipid profile in post-menopausal women, thus contributing to reduce their cardiovascular risk.

Brachial Artery↗

PubMed2003

Relation between conduit vessel stiffness (assessed by tonometry) and endothelial function (assessed by flow-mediated dilatation) in patients with and without coronary heart disease.

Endothelial dysfunction and large artery stiffness occur in patients with risk factors for coronary artery disease (CAD) and in those with established CAD. We evaluated the relation between endothelial function and conduit vessel distensibility in normal subjects, in patients with documented stable CAD, and in patients demonstrating only risk factors but no overt atherosclerosis. Endothelium-dependent dilatation was evaluated by way of flow-mediated dilatation of the brachial artery using high-resolution ultrasound. Large artery stiffness was assessed using tonometry. After adjusting for age and intergroup differences, percent flow-mediated dilatation showed statistically significant correlations with several measures of stiffness, including central pulse pressure (r = -0.457, p = 0.019), central systolic pressure (r = -0.442, p = 0.024), peripheral pulse pressure (r = -0.393, p = 0.039), peripheral systolic pressure (r = -0.398, p = 0.036), and proximal aortic compliance (r = 0.390, p = 0.049). Measures of arterial stiffness correlate significantly with those of endothelial function. An increase in large conduit vessel stiffness may represent either a cause or consequence of endothelial dysfunction and may explain why elevated pulse pressure is a new cardiovascular risk factor.

Adult↗

PubMed2004

An age-related decline in endothelial function is not associated with alterations in L-arginine transport in humans.

OBJECTIVES: Endothelial dysfunction is established in aged individuals; however, the mechanism(s) are not fully elucidated. We have previously identified l-arginine transport as a potential rate-limiting factor in nitric oxide (NO) production in heart-failure patients, characterized with endothelial dysfunction. We therefore aimed to investigate whether the age-related decline in endothelial function is due to reduced transport of the NO precursor, L-arginine. METHODS: Thirty-seven healthy males aged between 19 and 69 were recruited. Throughout 40 min of intra-arterial (i.a.) infusion of [3H]L-arginine (100 nCi/min), venous blood samples were withdrawn for the determination of L-arginine clearance. Venous occlusion plethysmography was then used to record the forearm blood flow responses to i.a. infusions of acetylcholine (ACh; 9.25 and 37 microg/min) and sodium nitroprusside (SNP; 2 and 8 microg/min). RESULTS: While ACh-induced vasodilation decreased with age (37 microg/min; young 15.87 +/- 1.30, middle-aged 9.59 +/- 1.33, older 10.42 +/- 1.12 ml/min per 100 ml tissue; P = 0.001), there was no change in forearm [3H]L-arginine clearance (young 126.08 +/- 19.05, middle-aged 122.47 +/- 20.96, older 126.56 +/- 19.56 ml/min; NS). Further [3H]L-arginine uptake studies in isolated peripheral blood mononuclear cells supported our in vivo findings, demonstrating no difference in [3H]L-arginine transport across the age spectrum. CONCLUSIONS: The present study excludes the hypothesis of impaired L-arginine transport as a potential mechanism for the age-related decline in endothelial function.

Acetylcholine↗

PubMed2000

Cholesterol-lowering treatment is associated with improvement in coronary vascular remodeling and endothelial function in patients with normal or mildly diseased coronary arteries.

Coronary vascular remodeling and altered endothelial function have been described in the early stages of native atherosclerosis. The purpose of this study was to evaluate the association between cholesterol-lowering therapy and coronary vascular remodeling and endothelial function in patients with normal or mildly diseases coronary arteries. Patients (N=101) with normal or mildly diseased coronary arteries by coronary angiography underwent intravascular ultrasound examination of the left anterior descending coronary artery. Vessel and lumen area, atherosclerotic plaque area, and plaque morphology were evaluated. Vascular reactivity was examined with the use of intracoronary adenosine, acetylcholine, and nitroglycerin. Patients were divided into 3 groups based on the total cholesterol levels: group 1 (n=25), patients with a history of hypercholesterolemia adequately treated (total cholesterol <240 mg/dL); group 2 (n=26), patients with hypercholesterolemia not adequately controlled (total cholesterol >/=240 mg/dL); and group 3 (n=50), patients without hypercholesterolemia. Vessel area and lumen area were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: vessel area 11.9+/-0.5, 10.6+/-0.4, and 11.8+/-0.4 mm(2), both P<0.05; lumen area 8.3+/-0.4, 6.9+/-0.3, and 8.9+/-0.3 mm(2), both P<0.01). However, plaque areas in groups 1 and 2 were similar. Furthermore, acetylcholine-induced percent increases in coronary blood flow were significantly greater in groups 1 and 3 than in group 2 (for respective values in groups 1, 2, and 3: 70.5+/-20.1%, 22.8+/-13.7%, and 68.6+/-14.8%, both P<0. 05). Cholesterol-lowering treatment is associated with an improvement in coronary lumen area that results not from a decrease in plaque area but from an increase in vessel area, reflecting vascular remodeling. Additionally, this adaptive process may occur in association with an improvement of endothelium-dependent vasodilation of the resistance coronary artery.

Anticholesteremic Agents↗

PubMed2004

Changes of homocysteine levels and arterial endothelial function in patients with high risk of coronary artery disease after 6-month folic acid supplementation.

OBJECTIVES: This study aimed to assess whether folic acid supplementation could produce longer-term (6-month) improvements in homocysteine levels and arterial endothelial function in patients with a high risk (3 or more traditional risk factors) of coronary artery disease (CAD) and hyperhomocysteinaemia. METHODS: Thirty-one adults with 3 or more traditional risk factors of CAD and hyperhomocysteinaemia were selected, without CAD (the criterion of CAD is that more than one main vessel has an obstruction > or = 50%) by coronary angiography. All subjects were given folic acid (5 mg/day) for 6 months. Fasting plasma homocysteine levels were measured by high-performance liquid chromatography. Plasma folic acid and vitamin B12 levels were measured with immunoassay. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound. RESULTS: Folic acid supplementation for 6 months was associated with a significant increase in mean (+/- SD) plasma levels of folic acid (4.6 +/- 1.4 microg/l to 9.1 +/- 2.5 microg/l; P < 0.01) and a significant decline in homocysteine levels (18.3 +/- 3.9 micromol/l to 11.5 +/- 2.8 micromol/l; P < 0.01). Flow-mediated dilation also improved significantly, from 6.8% +/- 2.1% to 8.9% +/- 1.7% (P < 0.01). CONCLUSION: These results demonstrate that long-term (6-month) folic acid administration significantly declines homocysteine levels and improves arterial endothelial function and has potential implications for the prevention of atherosclerosis in adults with 3 or more traditional risk factors of CAD and hyperhomocysteinaemia.

Aged↗

PubMed2006

[Beneficial effects of probucol on endothelial function in patients with acute coronary syndrome].

OBJECTIVE: The study investigate the antioxidant probucol on endothelial function in patients with acute coronary syndrome (ACS). METHODS: A total of 49 ACS patients randomly received standard therapy plus probucol (P, n = 24) or standard therapy (C, n = 25). Plasma oxidized low-density lipoprotein (ox-LDL), nitric oxide (NO) and circulating endothelial cells (CEC) were measured. The brachial arterial hyperemia-induced flow mediated dilation (FMD) and sublingual nitroglycerin (NTG) mediated vasodilatations were measured by high resolution ultrasound. These variables were analyzed before and after 3 months therapy. RESULTS: Plasma NO and FMD was significantly increased after 3 months therapy than before therapy [(80.46 +/- 10.24) micromol/Lvs (48.46 +/- 12.24) micromol/L, P < 0.01; (13.46 +/- 1.20)% vs (7.45 +/- 1.02)%, P < 0.05, respectively], while the number of CEC and ox-LDL were significantly decreased (P < 0.01) in P group. These values were similar before and after 3 months in C group. The linear correlation analysis showed that plasma ox-LDL negatively correlated with NO (r = -0.574, P < 0.01) and FMD (r = -0.517, P < 0.01) and positively correlated with CEC (r = 0.385, P < 0.01) in patients received 3 months probucol therapy. CONCLUSIONS: Chronic antioxidant probucol therapy could improve endothelial function in patients with ACS.

Adult↗

PubMed2000

Effects of occlusion devices for minimally invasive coronary artery bypass surgery on coronary endothelial function of atherosclerotic arteries.

BACKGROUND: During minimally invasive coronary artery bypass grafting surgery, technical devices are required to obtain an optimal operative field. However, these devices can cause lesions to the endothelium. Previous studies of the effect of devices on coronary endothelial function have been performed on normal coronary arteries. Balloon denudation is followed by regeneration of the endothelium, which is dysfunctional and by intimal hyperplasia resembling atherosclerosis. The Anastaflo (Baxter, Mississauga, Ontario, Canada) shunt is a surgical device used during the performance of coronary anastomoses that allows a continuous flow inside the artery during the surgery. METHODS: We compared the effects of three commonly used techniques on endothelial function: 1) using the Anastaflo shunt, 2) using Retract-o-tape (Genzyme, Cambridge, MA) silicone air cushion snaring, and 3) using a bulldog clamp on arteries submitted to balloon denudation 30 days prior to the surgical experiment on an in vivo model of beating heart off-pump coronary artery bypass (OPCAB). Balloon denudation was performed on the left anterior descending artery and on the right coronary artery. The devices were applied for 15 minutes on porcine epicardial coronary arteries, on the beating heart, after median sternotomy. Denuded control rings were taken at the site of denudation on which no devices were applied while non-denuded control rings were taken from the left circumflex artery. The endothelial function of control and instrumented arterial rings was studied in organ chambers filled with a modified Krebs-Ringer bicarbonate solution. After contraction to prostaglandin F(2)alpha, endothelium-dependent relaxation to serotonin (an agonist coupled to Gi-proteins) and bradykinin (a non-Gi-protein coupled agonist) were compared in the shunting group, the snaring group, the clamping group, and in controls. RESULTS: There was a significant decrease in the relaxations to serotonin and bradykinin in the denuded control group compared with the non-denuded control group, confirming that balloon denudation caused an endothelial dysfunction. However, there was no significant difference between the denuded control group and the hemostatic device groups (shunting, snaring and clamping) in the relaxation to serotonin. CONCLUSION: These results suggest that hemostatic devices used for OPCAB do not cause any greater injury in atherosclerotic coronary arteries already harbouring an endothelial dysfunction. The effects on platelet aggregation, intimal dissection, and plaque rupture remain to be determined.

Analysis of Variance↗

PubMed2006

Impaired systemic endothelial function in patients with pseudoexfoliation syndrome.

Pseudoexfoliation syndrome (PEX) is the most common clinical precursor of open-angle glaucoma. Recent studies have shown that pseudoexfoliative material is widely distributed throughout the body, including blood vessels. The aim of our study was to evaluate endothelial function in the brachial artery of patients with pseudoexfoliation syndrome. We prospectively examined 23 patients with PEX (mean age, 70 +/- 8 years) and 20 healthy age- and sex-matched individuals (mean age, 68 +/- 9 years) as a control group. Brachial artery endothelial function was assessed by vascular response to reactive hyperemia (flow-mediated dilation (FMD) and sublingual nitroglycerin (NTG-mediated dilation) using high-resolution ultrasound. Flow-mediated and NTG-induced dilation were expressed as the percent change in diameter after reactive hyperemia and after NTG administration relative to the baseline value, respectively. Patients with cardiovascular disease and other conditions associated with endothelial dysfunction were excluded. When compared with controls, patients with PEX had significantly lower flow-mediated dilation (4.5 +/- 2.8 versus 8.2 +/- 3.7, P = 0.01) and NTG-mediated dilation (10.9 +/- 3.1 versus 15.8 +/- 3.8, P = 0.0001). Flow-mediated dilation and NTG-mediated dilation were similar in PEX patients with glaucoma (n = 11) and without glaucoma (n = 12). Flow-mediated and NTG-mediated dilation did not correlate with any measured parameter in any patient or control subject. The findings indicate that systemic endothelial function is impaired in PEX syndrome patients.

Aged↗

PubMed2004

Active but transient improvement of endothelial function in rheumatoid arthritis patients undergoing long-term treatment with anti-tumor necrosis factor alpha antibody.

OBJECTIVE: Cardiovascular disease is the major cause of excessive mortality in rheumatoid arthritis (RA). Atherosclerosis and RA share similar inflammatory mechanisms that include involvement of tumor necrosis factor alpha (TNF alpha). Anti-TNF alpha antibody improved endothelial function in RA patients after a 12-week treatment. The aim of the present study was to assess whether improvement of endothelial function is still effective in long-term infliximab-treated RA patients. METHODS: Seven RA patients (5 women; age range 25-73 years) were studied. They had been treated with infliximab for at least 1 year and were currently being treated with this drug every 8 weeks. Endothelial-dependent and independent vasodilatation were measured by brachial ultrasonography. RESULTS: Following infliximab infusion, a rapid increase in the percentage of endothelial-dependent vasodilatation was found in all patients (mean +/- SD 9.4 +/- 5.5% 2 days postinfusion compared with 2.8 +/- 2.5% 2 days before infusion). However, values returned to baseline by 4 weeks after infusion. There were no differences in the percentage of endothelial-independent vasodilatation prior to and after infusion. A decrease in the individual disease activity score for each patient was observed at day 7 postinfusion (P = 0.02). CONCLUSION: Our study confirms an active but transient effect of infliximab on endothelial function in RA patients treated periodically with this drug. It may support long-term use of drugs that block TNF alpha function to reduce the high incidence of cardiovascular complications in RA.

Adult↗

PubMed2005

Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial.

OBJECTIVES: The UK Prospective Diabetes Study (UKPDS) showed that treatment with metformin decreases macrovascular morbidity and mortality independent of glycaemic control. We hypothesized that metformin may achieve this by improving endothelial function and chronic, low-grade inflammation. Data on this issue are scarce and we therefore tested, in the setting of a randomized, placebo-controlled trial, whether metformin can affect endothelial function and low-grade inflammation. DESIGN: The Hyperinsulinaemia the Outcome of its Metabolic Effects (HOME) trial is a double-blind trial, in which all patients were randomized to receive either metformin or placebo in addition to insulin therapy. At the beginning and the end of a 16-week treatment period fasting blood samples were drawn and a physical examination was carried out. SETTING: The trial was conducted in the outpatient clinics of three nonacademic hospitals (Hoogeveen, Meppel and Coevorden; the Netherlands). SUBJECTS: Patients were included if they were between 30 and 80 years of age; had received a diagnosis of diabetes after the age of 25; had never had an episode of ketoacidosis; and their blood glucose-lowering treatment previously consisted of oral agents but now only consisted of either insulin (n = 345) or insulin and metformin (n = 45). We excluded pregnant women and women trying to become pregnant, patients with a Cockroft-Gault-estimated creatinine clearance <50 mL min(-1), or low plasma cholinesterase (reference value <3.5 units L(-1)), patients with congestive heart failure (New York Heart Association class III/IV), or patients with other serious medical or psychiatric disease. A total of 745 eligible patients were approached; 390 gave informed consent and were randomized (196 metformin, 194 placebo). About 353 patients completed 16 weeks of treatment (171 metformin, 182 placebo). MAIN OUTCOME MEASURES: The HOME trial was designed to study the metabolic and cardiovascular effects of metformin during a follow-up of 4 years. Presented here are the results of an interim analysis after 16 weeks of treatment. RESULTS: When compared with placebo, metformin treatment was associated with an increase in urinary albumin excretion of 21% (-1 to +48; P = 0.06); a decrease in plasma von Willebrand factor of 6% (-10 to -2; P = 0.0007); a decrease in soluble vascular cell adhesion molecule-1 of 4% (-7 to -2; P = 0.0002); a decrease in soluble E-selectin of 6% (-10 to -2; P = 0.008); a decrease in tissue-type plasminogen activator of 16% (-20 to -12; P < 0.0001); and a decrease in plasminogen activator inhibitor-1 of 20% (-27 to -10; P = 0.0001). These changes could not be explained by metformin-associated changes in glycaemic control, body weight or insulin dose. Markers of inflammation, i.e. C-reactive protein and soluble intercellular adhesion molecule-1, did not change with metformin treatment. CONCLUSIONS: In patients with type 2 diabetes treated with insulin, metformin treatment was associated with improvement of endothelial function, which was largely unrelated to changes in glycaemic control, but not with improvement of chronic, low-grade inflammation.

Adult↗

PubMed2006

[Effect of statin treatment begun early after acute myocardial infarction on endothelial function in patients with normal levels of cholesterol. VAATOPE Study (VAlue of ATOrvastatin in Postinfarction Endothelium)].

BACKGROUND AND OBJECTIVE: Recent studies have suggested that statins reduce the rate of subsequent coronary events when these drugs are indicated early alter an acute coronary event. One potential mechanism by which these drugs might reduce the likelihood of such events is by enhancing endothelial function. The aim of this study was to determine whether early cholesterol reduction with atorvastatin improved endothelial function after acute myocardial infarction in patients with normal cholesterol levels. PATIENTS AND METHOD: Patients with a first acute myocardial infarction and normal levels of cholesterol were assigned to treatment with 10 mg atorvastatin (n = 15) or placebo (n = 15) for 8 weeks. Patients who had previously received treatment with statins were excluded. Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilation and response to endothelium-independent nitroglycerin. Total and LDL cholesterol levels and the distribution of risk factors were similar on admission and before randomization in both groups. All patients were assessed between 5 and 7 days postinfarction and after 8 weeks. RESULTS: Total and LDL cholesterol levels were significantly decreased after atorvastatin treatment. Total cholesterol decreased by 11% (p < 0.01) and LDL cholesterol by 18% (p < 0.01). Without atorvastatin flow-mediated dilation was unchanged (mean [SEM] 9.3 [1.7%] to 10.6 [1.7%]) but it increased with atorvastatin (8.9 [1.4%] to 16.5 [1.7%], p < 0.05). The response to nitroglycerin was similar in both groups during the period of study. CONCLUSIONS: The early administration of atorvastatin appears to enhance endothelial function in patients with acute myocardial infarction and normal levels of cholesterol.

Aged↗

PubMed1998

Endothelial function and dysfunction in heart failure.

The endothelium controls vascular smooth muscle tone by secreting substances that cause relaxation and contraction. Under physiological, basal conditions the endothelium constantly releases nitric oxide, a process closely regulated by the effect of shear stress on endothelial cells. Recent data raise the possibility that, among many other substances, bradykinin also plays an important role in the regulation of vascular tone. Bradykinin is a vasodilator that increases the activity of constitutive nitric oxide. Congestive heart failure (CHF) is a complex clinical syndrome in which abnormal vascular endothelial function has been shown to occur at both the experimental and clinical level. The reduced nitric oxide-mediated vasodilation in CHF is multifactorial. Constitutive nitric oxide synthase is downregulated as shear stress is reduced. Vascular angiotensin-converting enzyme (ACE), which produces angiotensin II and inactivates bradykinin, is up-regulated. Angiotensin II is a powerful vasoconstrictor, and the reduced availability of bradykinin will further down-regulate constitutive nitric oxide synthase. The CHF-induced activation of tumour necrosis factor also leads to a down-regulation of constitutive nitric oxide synthase and to an increased rate of endothelial-cell apoptosis. These observations suggest that abnormalities of endothelial function in CHF may contribute to increased peripheral vasomotor tone both at rest and during exercise, and raise the possibility that the beneficial effects of ACE inhibition in CHF may be due in part to improved endothelial function.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Effect of renal transplantation on endothelial function in haemodialysis patients.

BACKGROUND: Haemodialysis patients (HD) have been characterized by a high incidence and prevalence of atherosclerotic cardiovascular disease. Based on the traditional cardiovascular risk factors in this population, we cannot explain this high incidence and prevalence. One of the mechanisms contributing to cardiovascular risk in HD patients may be to uraemic toxins. Cardiovascular risk factors and uraemic toxins themselves may cause endothelial dysfunction, which may play a pivotal role in the development and progression of atherosclerosis in this population. We hypothesized that elimination of uraemic toxins in response to renal transplantation (RTx) can improve endothelial function as assessed by flow-mediated dilatation of brachial artery in haemodialysis (HD) patients. METHODS: Endothelial function measured by flow-mediated dilatation of the brachial artery (FMD) and glyceryltrinitrate-induced dilatation of the brachial artery (NMD) were assessed twice, during haemodialysis treatment and after RTx in 30 chronic haemodialysis patients. All patients were characterized by absence of known atherosclerotic disease and traditional cardiovascular risk factors. We also studied age- and gender-matched 20 normotensive healthy controls. RESULTS: FMD values significantly improved after RTx (6.69+/-3.1% vs 10.50+/-3.0%, P<0.001) in HD patients. FMD of patients both during haemodialysis and after RTx was lower than in healthy controls (6.69+/-3.1%, 10.50+/-3.0% vs 14.02+/-2.3%, P<0.001 and P<0.01, respectively). There was no change in NMD values after RTx in HD patients (16.27+/-1.9% vs 16.30+/-1.8%, P>0.05). Also, NMD values in all patients were similar to healthy control values. CONCLUSIONS: There is an improvement of endothelial function as assessed by FMD of the brachial artery after RTx in HD patients. This may be attributed to the elimination of uraemic toxins by successful RTx.

Adult↗

PubMed1999

Effects of leukocyte-depleted warm blood cardioplegia on cardiac and endothelial function.

It has been reported that neutrophils and platelets have deleterious effects on myocardium and endothelium during and after ischemia. In this study we evaluated the effects of a leukocyte-depleting filter (Sepacell PLX, Asahi medical, Tokyo) during warm blood cardioplegia and early reperfusion on cardiac and endothelial function in the blood-perfused rat heart. Hearts (n = 7 per group) from donor rats were excised and perfused with blood at 37 degrees C from a support rat. After 10 min of stabilization, the hearts were arrested for 60 min with warm blood cardioplegia given at 20 min intervals. This was followed by 60 min of reperfusion. A leukocyte-depleting filter was used during the cardioplegia and the initial 10 min of reperfusion in the experimental group (Group F) and it was not used in the control group (Group N). Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximum rate of left ventricular pressure rise (+dp/dt) and maximum rate of left ventricular pressure fall (-dp/dt) were measured as indices of left ventricular function before and after cardioplegic arrest. Coronary sinus effluent was obtained and the levels of MB isozyme of creatine kinase (CKMB), malondialdehide (MDA), elastase and thromboxane B2 (TXB2) were measured as indices of myocardial and endothelial injury. After 60 min of reperfusion, acetylcholine (Ach.) was administered to the coronary perfusate and the difference of nitric oxide (NO) concentration between inflow and outflow, and coronary blood flow were measured as an indication of endothelial function. Group F showed significantly lower LVEDP than Group N at 10 min of reperfusion. The elastase levels were significantly (p < 0.05) lower and the CKMB levels tended (p < 0.1) to be lower in Group F at 60 min of reperfusion. The administration of Ach. to the coronary perfusate showed significantly (p < 0.05) greater coronary blood flow and NO production in Group F. The results suggested that the use of a leukocyte-depleting filter during warm blood cardioplegia and early reperfusion preserves endothelial function and left ventricular diastolic compliance. The technique may provide beneficial effects by reducing reperfusion injury in patients undergoing cardiac surgery.

Animals↗

PubMed2006

ACE inhibition with perindopril and endothelial function. Results of a substudy of the EUROPA study: PERTINENT.

OBJECTIVES: EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease [EUROPA] demonstrates reduction in cardiovascular mortality and myocardial infarction for a possible vascular and antiatherosclerotic effect of angiotensin-converting enzyme (ACE) inhibition with perindopril. Our objective was to study the effect of perindopril on endothelial function and to verify its link to risk and occurrence of cardiovascular events. METHODS: Blood from 1200 EUROPA patients was withdrawn at baseline and after 1 year of treatment with either perindopril or placebo to measure von Willebrand factor and from 45 healthy subjects and 87 EUROPA patients to study endothelial function at the cellular level by cultivating in vitro human umbilical vein endothelial cells. In this setting, we determined protein expression/activity of endothelial nitric oxide synthase and the rate of apoptosis. Plasma levels of angiotensin II, bradykinin, tumor necrosis factor alpha, and nitrite/nitrate were also measured. RESULTS: The occurrence of cardiovascular events was related to von Willebrand factor at baseline (P = 0.013) that also significantly decreased after 1 year's treatment (P < 0.001). Perindopril upregulated 19% and 27% protein expression/activity of endothelial nitric oxide synthase (P < 0.05) as well as reduced the rate of apoptosis by 31% (P < 0.05). There was also a significant reduction in levels of angiotensin II, increase in bradykinin, reduction in tumor necrosis factor alpha, and increase in nitrite/nitrate (P < 0.05 for all). CONCLUSIONS: Abnormal endothelial function occurs in patients with coronary artery disease, and this can be counteracted by angiotensin-converting enzyme inhibition with perindopril. These effects could contribute, at least in part, to explaining the results of the main EUROPA Study.

Aged↗

PubMed2002

Isoflavone supplementation and endothelial function in menopausal women.

OBJECTIVE: Despite strong observational evidence for a beneficial role of oestrogen in cardiovascular disease, recent trial results suggest that hormone replacement therapy (HRT) may have adverse effects in menopausal women with established coronary heart disease. Isoflavones are oestrogen analogues found in plants with oestrogen-like properties and, because of a favourable side-effect profile, may be ideal alternatives to HRT with respect to cardiovascular benefits. Endothelial function is a marker of cardiovascular health. We aimed to determine the effect of isoflavones on endothelial function using the brachial artery reactivity test. DESIGN AND MEASUREMENTS: Twenty-nine healthy menopausal women underwent entry and exit brachial artery reactivity testing following randomization to 2 weeks of an oral soy isoflavone concentrate containing 80 mg of soy isoflavones (Archer Daniel Midland Inc., IL, USA) or placebo. RESULTS: At study exit, there was no difference between placebo and isoflavone groups with respect to flow-mediated dilation (%FMD(max)), change (entry to exit) in %FMD(max) or response to nitroglycerine (%TNG). Subgroup analyses assessing lipid and oestrogen effects did not produce any significant results. CONCLUSIONS: These results suggest that short-term oral isoflavone supplements do not improve endothelial function in healthy menopausal women.

Administration, Oral↗

PubMed1998

Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model.

OBJECTIVE: Previous studies suggested that endothelin-1 (ET-1) may play a pathophysiological role in myocardial ischemia/reperfusion injury. This study was designed to investigate the effects of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia in a heterotopic rat heart transplantation model. METHODS: Isogenic intraabdominal heterotopic transplantation was performed in Lewis rats. After 1 h of cold ischemic preservation reperfusion was started either after application of placebo (control), BQ123 (3 mumol/kg/min). BQ788 (3 mumol/kg/min), ET-1 (8 pmol/kg/min) or simultaneous infusion of BQ123 or BQ788 and ET-1, respectively (n = 12 each). An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Myocardial blood flow (MBF) was assessed by the hydrogen-clearance method. Measurements were taken after 1 and 24 h of reperfusion. Endothelium-dependent vasodilation to acetylcholine (ACH) and endothelium-independent vasodilation to sodium nitroprusside were also determined. RESULTS: Both BQ123 and BQ788 significantly improved myocardial and endothelial functional recovery during early reperfusion, whereas ET-1 significantly impaired myocardial and endothelial function. Simultaneous infusion of ET-1 diminished the effects of BQ123 and BQ788. Although myocardial function and baseline MBF were similar in all groups after 24 h of reperfusion, endothelium dependent vasodilation to ACH was still significantly higher in the BQ123 and BQ788 groups and lower in the ET-1 groups (p < 0.05). CONCLUSIONS: These results suggest that endogenous ET release is involved in the pathogenesis of reperfusion injury after heart transplantation. ET-A and ET-B receptor antagonists may be useful to reduce ischemia/reperfusion injury.

Acetylcholine↗

PubMed1997

Endothelial function. General considerations.

The endothelium is involved in both the physiological regulation of vascular tone and the structural transformation of the vessel under pathological conditions. Under physiological conditions, endothelial cells continuously secrete nitric oxide (NO), which relaxes smooth muscle cells and ensures vessel patency. Damaged or excessively activated endothelial cells can also secrete vasoconstrictor factors, the best known of which is endothelin-1 (ET-1), as well as factors that affect the differentiation and growth of vascular smooth muscle cells. How endothelial cell damage contributes, under pathological conditions, to vascular disease can best be illustrated in patients with diabetes mellitus, in whom there are pronounced changes in endothelial cell structure and function. Endothelial cells also interact with cells in the bloodstream, ET-1 and other factors are released from endothelial cells into the bloodstream, where their chemotactic action can induce leucocytes and platelets to migrate to the endothelial wall. Endothelial cells induce adhesion by expression of specific surface adhesion molecules (selectins, integrins and a supergene family of immunoglobulins) that can interact with ligands on the leucocytes and platelets. The expression of adhesion molecules is increased in endothelial cells chronically damaged by risk factors for atherosclerosis. The disturbed permeability of the endothelial layer in patients with diabetes mellitus and/or hyperlipidaemia leads to an increased influx of substances from the circulation into the vessel wall. In addition, endothelial cell dysfunction can lead to accelerated intravessel blood coagulation. It is evident that the endothelium plays a central role in many of the early pathophysiological processes involved in atherosclerosis. It is therefore important to investigate the effects of antiatherosclerotic therapy on endothelial cell function and cell-to-cell interactions. Until recently, little was known about the direct effects of calcium antagonists on endothelial cell function. Recent studies, including two clinical studies, indicate that calcium antagonists primarily affect interactions of endothelial cells, smooth muscle cells, monocytes and platelets, which play a central role in the early phases of the development of atherosclerosis, whereas the protective effect of these agents on the vascular system appears to be low at later stages.

Animals↗