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Results for “Endothelial function”

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At least 523 records · Page 29Linked to original sources

PubMed2001

Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin.

Patients with heterozygous familial hypercholesterolemia (hFH) are at very high risk for premature coronary heart disease. In the last decade, treatment with statins has reduced cardiovascular mortality in these patients. The aim of this study was to analyze arterial endothelial function assessed as flow-mediated dilatation (FMD) and soluble E-selectin (sE-selectin) levels in patients with hFH under a long-term lipid-lowering treatment. Twenty-five patients who completed the study received a dose of simvastatin to achieve a treatment goal of at least 30% reduction in serum low-density lipoprotein (LDL)-cholesterol (LDL-C) for 52 weeks. Functional and biochemical measurements were taken at entry, and at week 12 and 52 of treatment. FMD was measured by vascular ultrasound of the brachial artery. sE-selectin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 were determined by enzyme linked immunosorbent assay (ELISA). LDL-C levels were significantly reduced by treatment at week 12 and maintained at week 52 (reduction vs. baseline, 44+/-12 and 43+/-11%, respectively, P<0.0001). A significant improvement in endothelial function, measured as FMD (baseline, 4.7+/-6.2%; 12 weeks, 12.3+/-5.9%; 52 weeks, 9.7+/-4.7%; P<0.005) and a reduction in sE-selectin levels (baseline, 16.2+/-3.4 ng/ml; 12 weeks, 11.0+/-3.2 ng/ml; 52 weeks, 12.3+/-4.2 ng/ml; P<0.01) were observed. Endothelial-independent relaxation induced by nitroglycerin was not modified during the study. Our results indicate that a long-term treatment with simvastatin produced a sustained beneficial effect in endothelial function in hFH patients.

Adult↗

PubMed2002

Improvement of Endothelial Function by HMG-CoA Reductase Inhibitors.

Endothelial dysfunction is the early and crucial state of atherosclerosis that is associated with a poor prognosis. Mechanistically, endothelial dysfunction is caused by reduced nitric oxide bioactivity. HMG-CoA reductase inhibitors (statins) effectively lower cholesterol plasma levels and profoundly decrease the cardiovascular risk of hypercholesterolemic patients. It is well established that statins improve endothelial dysfunction in those patients. The underlying mechanisms are less clear. It is thought that pleiotrophic, cholesterol-independent effects of statins such as increase of nitric oxide bioactivity and reduction of oxidative stress may contribute to the vasoprotective effects of statins. Therefore, it is speculated that statins, at least in part, improve endothelial function independent of plasma cholesterol concentrations and may thereby exert beneficial clinical effects. This notion of statins as general atheroprotective drugs has been underlined by in vitro experiments, animal studies and small clinical trials. However, large-scale clinical intervention studies are needed to confirm a positive influence of statins on endothelial dysfunction and cardiac event rates in normochlesterolemic patients. (c) 2002 Prous Science. All rights reserved.

Journal Article↗

PubMed1993

Impairment of vascular endothelial function by high-potassium storage solutions.

High-potassium cold storage solutions are currently used to preserve myocardial function during heart transplantation. However, the effects of high potassium concentration on vascular endothelial function are not well known. We therefore tested vascular rings for endothelial-dependent and endothelial-independent relaxation during storage in normokalemic, normothermic buffers and then in buffers supplemented with 10 to 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced at all high potassium concentrations. Endothelial-independent relaxation was impaired only with 80 and 110 mmol/L KCl buffers. Both endothelial-dependent relaxation and endothelial-independent relaxation returned to normal values after washout of excess potassium. Similarly, endothelial-dependent relaxation and endothelial-independent relaxation were assessed in rings after 24 hours of hypothermic storage in normokalemic Krebs buffer, and in buffers containing 20 and 110 mmol/L KCl. Maximal endothelial-dependent relaxation was significantly reduced after preservation in the high-potassium solutions, whereas endothelial-independent relaxation was not impaired. We conclude that there is significant impairment of endothelial function after cold storage in a high-potassium buffer. Inadequate washout of potassium during normothermic conditions may lead to further functional impairment of vascular responsiveness. A low-potassium storage medium is recommended for improved vascular protection.

Animals↗

PubMed2001

Tamoxifen is not detrimental to endothelial function in postmenopausal women with breast cancer.

BACKGROUND: Tamoxifen has mixed estrogen agonist and antagonist properties in estrogen-regulated tissues. Its effect on the cardiovascular system is not well defined. We carried out a study to investigate the effect of tamoxifen on peripheral vascular endothelial function. METHODS: Three groups of postmenopausal women (median age, 56 years; range, 39 to 69 years) with breast cancer were studied. Patients in group 1 (n = 10) were newly diagnosed with breast cancer and studied before and after 4 weeks treatment with tamoxifen. Group 2 women (n = 6) had been receiving long-term tamoxifen (3 to 5 years) and were studied while taking tamoxifen and 4 weeks after stopping it. The final group of 6 subjects were in remission from primary breast cancer and were not receiving or had previously received tamoxifen. Ultrasound assessments of endothelial function were done before and 4 weeks after the initiation or discontinuation of tamoxifen with the nontreatment group acting as control. All ultrasound imaging was made by a single investigator blinded to the therapeutic status of the subject. Brachial artery diameter was measured by ultrasound at baseline and 1 minute after reactive hyperemia. Flow-mediated reactivity (FMR) was defined as percent change in artery diameter from baseline 1 minute after reactive hyperemia. RESULTS: There was no change in FMR in patients before compared with 4 weeks after starting tamoxifen (4.06% +/- 1.44% vs 3.97% +/- 1.20%, respectively, mean +/- standard error of the mean [SEM], P =.97). There was no significant change in FMR on withdrawal from tamoxifen (1.84% +/- 1.98% vs -0.42% +/- 1.44% on tamoxifen vs off tamoxifen, mean +/- SEM, P =.36). FMR in subjects taking tamoxifen was no different from the control group (3.17% +/- 1.05% vs 3.16% +/- 0.91%, respectively, mean +/- SEM, P =.995). CONCLUSIONS: Tamoxifen does not appear to affect endothelial function in the short term in postmenopausal women with breast cancer.

Adult↗

PubMed2006

[Endothelial function evaluation in salt-sensitive normotensive and mild hypertensive subjects and effects of potassium supplement].

OBJECTIVE: Salt-sensitivity plays an important role in essential hypertension and is associated with more severe target organ injury and higher mortality in patients with essential hypertension. However, the pathologic mechanism of salt-sensitivity is poorly understood and endothelial dysfunction might be involved in salt-sensitive hypertension. We, therefore, observed the endothelial function changes by measuring plasma and urine nitric oxide (NO) concentrations in salt-sensitive (SS) normotensive and mild hypertensive subjects underwent various salt loading protocols and the effects of potassium supplement. METHODS: Thirty-nine normotensive and mild hypertensive subjects (< 160/100 mm Hg), aged 16-60, were enrolled and the study protocol is as follows: 3 days baseline investigation, 1 week low-salt loading (3 g/day), 1 week. high-salt loading (18 g/day) and 1 week high-salt loading plus potassium chloride (4.5 g/day). RESULTS: Plasma and urine NO levels were significantly lower in SS (n = 8) subjects at baseline, low-salt and high-salt loading phases compared with salt-resistant subjects (SR, n = 31) and oral potassium supplement to SS subjects with high salt loading significantly increased plasma and urine NO levels. CONCLUSION: Endothelial function is impaired in normotensive and mild hypertensive SS subjects. Oral potassium supplement could improve endothelial function in normotensive and mild hypertensive SS subjects.

Adult↗

PubMed2003

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) microg/L vs. (106.22 +/- 19.16) microg/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.

Adult↗

PubMed2003

The effect of calcium dobesilate on vascular endothelial function, blood pressure, and markers of oxidation in obese male smokers: a placebo-controlled randomised clinical trial.

This randomised double-blind, placebo-controlled, clinical trial investigated the effect of 3 months of treatment with calcium dobesilate on endothelium-dependent vasodilation, markers of endothelial function, blood pressure, and markers of oxidation in obese, male smokers. Vascular effects may depend on the type of vessel and we, therefore, investigated both smaller arteries, i.e. resistance arteries and small arterioles, and large conduit arteries. Vascular function was measured by acetylcholine- and sodium-nitroprusside-mediated vasodilation, and capillary recruitment, in the skin microcirculation; by forearm blood flow (FBF) responses to several agonists and to N-G-monomethyl L-arginine (L-NMMA) in the forearm vascular bed; by flow-mediated vasodilation in the brachial artery; and by determination of soluble levels of vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and E-selectin. Twenty-eight individuals received dobesilate and 24 placebo. No effect of calcium dobesilate on endothelial function, blood pressure or markers of oxidation was observed compared with placebo. The difference in acetylcholine-mediated vasodilation in the microcirculation was -52.1%-point (95% confidence interval -132.8 to 28.1); in sodium-nitroprusside-mediated vasodilation in the microcirculation, 2.6%-point (-95.1 to 100.2); in capillary recruitment, 2.5%-point (-6.8 to 11.7); in acetylcholine-induced increases in FBF (n=28), 23%-point (-173 to 126); in L-NMMA-induced reduction of basal FBF, -2.8%-point (-29.3 to 23.8); in flow-mediated vasodilation of the brachial artery, 0.3%-points (-2.7 to 3.3); in 24-h systolic blood pressure, 2.1 mmHg (-1.3 to 5.5); in soluble VCAM-1, 54 ng/ml (-8 to 115); in soluble ICAM-1, 9 ng/ml (-49 to 67); in sE-selectin, -17 ng/ml (-44 to 11); in ketocholesterol 5 nM (-17 to 26); and in oxidised LDL -1.6 U/l (-6.7 to 3.5). We have shown that endothelial function, blood pressure, and markers of oxidation were not affected by 3 months of treatment with calcium dobesilate in mildly obese, smoking men. Thus, our data provide no evidence of an effect on vascular function of calcium dobesilate in humans.

Adolescent↗

PubMed2004

Impact of prolonged cyclooxygenase-2 inhibition on inflammatory markers and endothelial function in patients with ischemic heart disease and raised C-reactive protein: a randomized placebo-controlled study.

BACKGROUND: The impact of cyclooxygenase (COX)-2 antagonist treatment on acute coronary risk is controversial. We investigated the effect of prolonged COX-2 inhibition on inflammatory profile and endothelial function in patients with ischemic heart disease and high serum C-reactive protein (CRP) values. METHODS AND RESULTS: In a double-blind study, 35 stable subjects on low-dose aspirin with > or =2 previous acute coronary events and 2 of 2 screening CRP values >2.0 mg/L were randomized to the COX-2 inhibitor rofecoxib (25 mg) or placebo daily for 6 months. Serum CRP, interleukin-6 (IL-6), P-selectin, matrix metalloproteinase-9 (MMP-9), and brachial artery endothelial function were evaluated. In the placebo group, CRP (median) was 3.16 mg/L (25% and 75% quartiles, 1.90 and 5.78 mg/L) at baseline and 4.22 mg/L (25% and 75% quartiles, 2.04 and 6.25 mg/L) at 6 months; in the rofecoxib group, CRP was 3.45 mg/L (25% and 75% quartiles, 2.08 and 5.78 mg/L) at baseline and 1.41 mg/L (25% and 75% quartiles, 1.17 and 4.81 mg/L) at 6 months (P=0.03). Rofecoxib compared with placebo also lowered IL-6 at 6 months (P=0.0002). There was a significant off-drug effect on CRP and IL-6 levels in the rofecoxib group 3 months after treatment (P=0.005 and P=0.009, respectively). Rofecoxib did not significantly affect P-selectin, MMP-9, and brachial artery vasoreactivity. CONCLUSIONS: Prolonged COX-2 inhibition attenuates CRP and IL-6, does not modify P-selectin and MMP-9, and has no deleterious effect on endothelial function in stable patients with a history of recurrent acute coronary events and raised CRP. These results strengthen the rationale for evaluating the clinical benefit of COX-2 inhibition in patients with ischemic heart disease.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMedDate not supplied

Effects of soy isoflavones on endothelial function in healthy postmenopausal women.

OBJECTIVE: To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women. DESIGN: Sixty naturally postmenopausal women were randomly assigned to receive isoflavone or placebo tablets for 6 months. Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and soluble thrombomodulin, von Willebrand factor, and tissue plasminogen activator. Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity parameters after reactive hyperemia and after sublingual administration of nitroglycerin; furthermore, in the active group, the effect of isoflavones was also evaluated during the intra-arterial infusion of N-monomethyl-L-arginine. Serum levels of lipids [high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides and lipoprotein(a)] and hemostatic factors (prothrombin, fibrinogen, plasminogen activator inhibitor-1, and fibrin D-dimer) were also measured. To confirm the absorption of isoflavones, their blood concentrations were determined. RESULTS: Isoflavone treatment versus placebo was associated with a significant improvement in endothelium-dependent vasodilatation but had no impact on endothelial-independent arterial diameter and flow. Intra-arterial infusion of N-monomethyl-L-arginine inhibited the significant effect of isoflavones on endothelium-mediated vasodilatation. Furthermore, isoflavone group experienced statistically significant reductions in plasma concentrations of ICAM-1, VCAM-1, and E-selectin. Levels of soluble thrombomodulin, von Willebrand factor, tissue plasminogen activator, lipids, and hemostatic factors did not change significantly throughout the study in both groups. CONCLUSIONS: Our findings suggest a positive influence of soy isoflavones on endothelial function in healthy postmenopausal women as evidenced by an improvement in endothelium-dependent vasodilatation and a reduction in plasma adhesion molecule levels.

Brachial Artery↗

PubMed2001

Venous endothelial function in postmenopausal women after six months of tibolone therapy.

STUDY OBJECTIVE: To test venous endothelial function in long-term climateric therapy with tibolone. DESIGN: Measurement of dorsal hand-vein diameter by venous occlusion plethysmography during infusion of norepinephrine (NE), bradykinin (BK), NG-monomethyl L-arginine (L-NMMA) and sodium nitroprusside (SNP). SETTING: Plethysmography and Menopause Units. University Hospital Valdecilla. Santander. Spain. PATIENTS: Eleven postmenopausal women having continuous treatment with oral tibolone (2.5 mg/day) for 6 months. INTERVENTIONS: Three plethysmography studies were made: at baseline, and at three and six months of treatment. MAIN OUTCOME MEASURES: Dorsal hand-vein diameter measured by venous occlusion plethysmography during infusion of NE, BK, L-NMMA and SNP. RESULTS: (a) Baseline study: maximum dilation with BK was 54.2+/-10.2%. (b) Three-month study: BK dilation of 71.5+/-11.9%, with a significant increase of 17.3% (P=0.019) compared with baseline. (c) Six-month study: BK dilation of 77.5+/-11.9%, with a significant increase 23.3% (P=0.002) compared with baseline. Maximal vasodilation was reached with SNP in the three studies and L-NMMA infusion has a similar vasoconstrictor response in the three studies. CONCLUSIONS: Long-term climateric therapy with tibolone improves vein endothelium-dependent vasodilation suggesting a positive impact of this drug on endothelial function.

Administration, Oral↗

PubMed2004

Xuezhikang, an extract of cholestin, protects endothelial function through antiinflammatory and lipid-lowering mechanisms in patients with coronary heart disease.

BACKGROUND: Endothelial dysfunction is associated with inflammation and postprandial hypertriglyceridemia. Xuezhikang, an extract of Cholestin, a dietary supplement, has lipid-modulating and antiinflammatory effects. We explored the effects of xuezhikang on endothelial function and high-sensitivity C-reactive protein (hs-CRP) in patients with coronary heart disease (CHD). METHODS AND RESULTS: We prospectively randomized 50 CHD patients to xuezhikang 1200 mg/d or placebo for 6 weeks. Fasting hs-CRP concentrations, flow-mediated vasodilation (FMD) at 0 and 4 hours, and lipid parameters at 0, 2, 4, and 6 hours were monitored after a high-fat meal (800 calories; 50 g fat) in all patients. All patients underwent a high-fat meal test at the beginning of the study and after 6 weeks of treatment. Postprandial FMD was significantly worse at 4 hours after a high-fat meal (P<0.05), and this was associated with the area under the triglyceride curve (TG-AUC) (r=0.345, P<0.01). After 6 weeks of xuezhikang, fasting hs-CRP levels and TG-AUC (P<0.001 for each) decreased. Furthermore, preprandial and postprandial FMD significantly improved (P<0.001). There were no significant changes in serum lipids and FMD in the placebo arm. In multivariable regression analysis, changes in TG-AUC and fasting hs-CRP levels were predictive of improvement in preprandial FMD (P<0.05). CONCLUSIONS: Xuezhikang effectively improved preprandial and postprandial endothelial function through its potent antiinflammatory and lipid-lowering effects.

Angina Pectoris↗

PubMed2001

Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.

Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unknown whether hypoglycemic drug therapy can modulate this abnormality. We studied patients with type 2 diabetes and stable ischemic heart disease (n = 28) and lean, healthy control subjects (n = 31). Forearm blood flow was measured by venous occlusion plethysmography during dose-response studies of acetylcholine (ACh) and sodium nitroprusside (SNP) infused into the brachial artery. In the patients and 10 healthy control subjects, ACh was repeated after intrabrachial infusion of insulin. Patients were restudied after 2 months of insulin therapy with four daily subcutaneous injections (treatment group, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high physiological levels (133 +/- 14.6 mU/l in patients) with a minor increase in systemic venous serum insulin. This increased the ACh response by 149 +/- 47, 110 +/- 33, 100 +/- 45, and 106 +/- 44% during the four ACh doses in healthy control subjects (P < 0.0001) but had no effect in patients (P = 0.3). After 2 months, HbA(1c) in the treatment group had decreased from 10.0 +/- 0.4 to 7.5 +/- 0.2%. Although neither the ACh response (P = 0.09) nor the SNP response (P = 0.4) had changed significantly, insulin stimulation had a significant effect, as the ACh response increased by 58 +/- 25, 84 +/- 66, 120 +/- 93, and 69 +/- 36% (P = 0.0002). In the time control group, insulin stimulation remained without effect after 8 weeks (P = 0.7). In conclusion, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.

Acetylcholine↗

PubMed2005

Plasminogen activator inhibitor-1 is associated with impaired endothelial function in women with systemic lupus erythematosus.

Endothelial function, measured noninvasively by brachial artery flow-mediated dilatation (FMD), has been shown to be impaired in patients with systemic lupus erythematosus (SLE). We hypothesized that depressed FMD in SLE patients is associated with increased levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis and regulator of vasoactivity. In this cross-sectional study of female SLE patients under the age of 55, putative markers of cardiovascular disease (CVD) such as PAI-1 were measured in addition to lupus-related disease activity (SLEDAI). The primary outcome, FMD, was measured using high-resolution ultrasound of the brachial artery gated to the R wave to determine endothelial-dependent vasomotion. Endothelial-independent vasomotion was measured in response to nitroglycerin (NMD). Seventy-six female SLE patients, mean age 38.3 +/- 9.4 years, were included. All patients demonstrated normal NMD responses, indicating that depression of FMD was related to decreased endothelial nitric oxide production. Increased PAI-1 was related to depressed FMD by univariate regression (P = 0.004). In a multivariable regression model adjusting for t-PA (tissue plasminogen activator)/PAI-1 ratio, SLEDAI, age at visit, family history of cardiovascular disease, SLE disease duration and body mass index, every 1 ng/mL increase in PAI-1 was associated with a reduction of 0.07 units FMD (P = 0.039). PAI-1 was associated with impaired endothelial dysfunction, after controlling for several potential confounders. Given the high incidence of cardiovascular disease in SLE, further investigation of the role of subclinical markers of CVD is needed.

Adult↗

PubMed2004

[Effect of aging on the endothelial function of the penile corpus cavernosum in rats].

OBJECTIVE: To evaluate the effect of aging on the endothelial function of the penile corpus cavernosum in rats. METHODS: The intracavernosal pressure (ICP) was compared in response to acetylcholine (Ach, endothelium-dependent vasodilator), sodium nitroprusside (SNP, an NO donor) and A23187 (a calcium ionophore)in the young (5 months old) and aged (20 months old) rats. In addition, the activity of nitric oxide synthase (NOS)in penile cavernosal tissues was examined. RESULTS: Ach-mediated ICP was significantly attenuated from the maximum of (54.8 +/- 4.2) in the young rats to (40.3 +/- 2.8) mm Hg in the aged ones (Ach = 0.1 mmol/L), P < 0.01. The ICP to SNP (0.1 mmol/L) was (58.9 +/- 4.7) mm Hg in the young rats and (51.7 +/- 5.3) mm Hg in the aged. No statistically significant difference was noted between the two groups, P > 0.05. The Ach-mediated ICP in the young rats was not significantly augmented from the maximum of (54.8 +/- 4.2) to (55.8 +/- 4.7) mm Hg in the presence of the calcium ionophore A23187 (10 micromol/L), P > 0.05. However, A23187 significantly augmented Ach-mediated ICP in the aged from the maximum of (40.3 +/- 2.8) to (56.2 +/- 4.1) mm Hg, P < 0.01. Finally the activity of nitric oxide synthase was not significantly attenuated in either the aged or the young, P > 0.05. CONCLUSION: The endothelial function of the penile cavernosum declines with the advance of age. And endothelial dysfunction may play some role in the mechanisms of age-related erectile dysfunction.

Aging↗

PubMed1994

Influence of lipoproteins on endothelial function.

The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. Nitric oxide is a potent vasodilator and inhibitor of platelet function which under most circumstances is released together with prostacyclin which exerts similar effects. Both substances play an important protective role in the coronary circulation in that they cause continuous vasodilation and inhibition of platelet function. In addition, the endothelium is a source of contracting factors such as endothelin-1, thromboxane A2 and endoperoxides. Due to its strategic anatomic position, the endothelium is a primary target of injuries and cardiovascular risk factors. Besides other risk factors such as hypertension and diabetes, low density lipoproteins alter endothelial function. A reduced release of endothelium-derived relaxing factors and an enhanced liberation of endothelium-derived contracting factors are common in the presence of lipoproteins. These alterations in endothelial function are likely to contribute to the pathogenesis as well as progression and complications of coronary artery disease such as vasospasm and thrombus formation. This review will focus on the influence of lipoproteins on endothelial function.

Animals↗

PubMed1998

Effects of atorvastatin monotherapy and simvastatin plus cholestyramine on arterial endothelial function in patients with severe primary hypercholesterolaemia.

Endothelial dysfunction is an important early event in atherogenesis. Changes in arterial endothelial physiology were studied in patients with severe primary hypercholesterolaemia participating in an ongoing clinical trial evaluating atorvastatin and simvastatin. Endothelial function was assessed non-invasively using brachial ultrasound and the primary outcome measure was flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperaemia. Patients were studied upon entry while still using simvastatin 40 mg daily and again after a 10-week washout (baseline). Over the next 30 weeks, 20 patients received atorvastatin titrated up to 80 mg daily and 12 patients received simvastatin titrated up to 40 mg daily (plus cholestyramine 4 g daily in 10/12), followed by a final ultrasound study. During simvastatin washout, total and low density lipoprotein (LDL) cholesterol rose by a median 23-29% and 30-34%, respectively. During atorvastatin therapy, total and LDL cholesterol fell by a median of 41 and 46%, respectively, triglycerides fell by 45%, and high density lipoprotein (HDL) cholesterol rose by 10%. During simvastatin plus cholestyramine therapy, the respective median changes were - 32, - 39, - 44 and + 11%. Patients at baseline showed evidence of impaired FMD and this improved significantly on either treatment, from a median + 2.2 to + 5.5% on atorvastatin and from + 1.8 to + 4.5% on simvastatin plus cholestyramine (P < 0.01 for both treatments). Typical response in healthy subjects would be from + 8 to + 9%. FMD at baseline was correlated with HDL cholesterol (r=0.49, P < 0.01). Change in FMD was inversely correlated with baseline FMD (r=-0.54, P < 0.001). Endothelial dysfunction in primary hypercholesterolaemia was improved by treatment with atorvastatin or simvastatin plus cholestyramine and this effect may result in the prevention of future coronary events.

Adult↗

PubMed2001

Endothelin receptor blockade improves endothelial function in human internal mammary arteries.

OBJECTIVE: Endothelial dysfunction, specifically endothelium-derived contracting factors have been implicated in the development of arterial conduit vasospasm. The potent vasoconstrictor endothelin-1 (ET-1) has received much attention in this regard. The present study was designed to evaluate the role of ET-1 in the development of endothelial dysfunction in human internal mammary arteries (IMA). To this aim, we examined the effects of specific and non-specific ET-receptor antagonists on endothelial function (assessed using acetylcholine (ACh)-induced vasodilation) in segments of IMA obtained during coronary artery bypass graft (CABG) surgery. METHODS: Vascular segments of IMA were obtained from 51 patients undergoing elective coronary artery bypass graft (CABG) surgery and in vitro endothelium-dependent and -independent responses to ACh and sodium nitroprusside (SNP) were assessed. Isometric dose response curves (DRC) to ACh and SNP were constructed in pre-contracted rings in the presence and absence of bosentan (ET(A/B) receptor antagonist, 3 microM), BQ-123 (ET(A) antagonist, 1 microM) and BQ-788 (ET(B) antagonist, 1 microM) using the isolated organ bath apparatus. Percent maximum relaxation (%E(max)) and sensitivity (pEC(50)) were compared between interventions. RESULTS: ACh caused dose-dependent endothelium-mediated relaxation in IMA (%E(max) 43+/-4, pEC(50) 6. 74+/-0.12). In the presence of bosentan, BQ-123 and BQ-788 ACh-induced relaxation was significantly augmented (%E(max) bosentan 60+/-3, BQ-123 56+/-4, BQ-788 53+/-5 vs. control 43+/-4, P<0.05) without affecting sensitivity. The effects of these antagonists were endothelium-specific since endothelium-independent responses to SNP remained unaltered. Furthermore, the beneficial effects were independently and maximally mediated by ET(A) and ET(B) receptors (%E(max) BQ-123 56+/-4 vs. BQ-788 53+/-5 vs. bosentan 60+/-3, P>0. 05). CONCLUSIONS: These data uncover, for the first time, beneficial effects of ET receptor blockade on endothelial-dependent vasorelaxation in human IMA.

Acetylcholine↗

PubMed2003

The acute effect of orlistat on endothelial function in young obese women.

Recent studies indicate that abdominal fat accumulation is related to impaired endothelial function in young healthy volunteers. The aim of this study was to determine the acute effect of gastrointestinal lipase inhibitor on brachial flow-mediated vasodilatation and hemodynamic parameters in young obese women. The study population was composed of 42 female obese patients (mean age 29 +/- 4 years, age range between 18 and 34 years). Flow-mediated endothelial-dependent vasodilatation was assessed in the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Brachial artery diameter (3.46 +/- 0.72 mm to 3.82 +/- 0.84 mm) and flow-mediated vasodilation (7.6 +/- 0.8% to 9.8 +/- 1.6%) changed significantly after 12 weeks of therapy (p < 0.001). Brachial artery flow was not changed (124 +/- 92 ml/min to 148 +/- 14 ml/min, p > 0.05). The results of this study demonstrate that orlistat improved endothelial function, weight, body mass index and systolic and diastolic blood pressure in young women.

Adult↗