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Results for “endothelial function”

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At least 253 records · Page 14Linked to original sources

PubMed2001

Dietary modulation of endothelial function: implications for cardiovascular disease.

The vascular endothelium is the primary site of dysfunction in many diseases, particularly cardiovascular disease. A variety of risk factors, including smoking, hypercholesterolemia, hyperhomocysteinemia, hypertension, and diabetes mellitus, adversely affect endothelial function. Emerging evidence suggests an important role of dietary factors in modulating endothelial function. In particular, n-3 fatty acids, antioxidant vitamins (especially vitamins E and C), folic acid, and L-arginine appear to have beneficial effects on vascular endothelial function, either by decreasing endothelial activation or by improving endothelium-dependent vasodilation in patients at high risk of cardiovascular disease as well as in healthy subjects. These effects may serve as one potential mechanism through which these nutrients reduce the risk of cardiovascular disease, as observed in epidemiologic studies and several clinical trials. This article reviews clinical and experimental evidence regarding the role of these nutrients in modulating endothelial function and their potential to prevent cardiovascular disease.

Antioxidants↗

PubMed2004

[Influence of tobacco smoking on endothelial function in lead-exposed male workers].

BACKGROUND: Endothelial dysfunction is a pathology resulting from smoking and occupational exposure to lead. The aim of the study was to examine the influence of cigarette smoking on biochemical parameters of endothelial function in people occupationally exposed to lead. MATERIALS AND METHODS: The study covered 105 men, including 43 lead exposed copper-smelters (mean age 49.9 +/- 4.1) and 62 non-exposed men (mean age 47.3 +/- 9.3) formed the control group. In all subjects, peripheral blood lipid concentrations, biochemical parameters of endothelial function (nitric oxide, endothelin-1, sICAM-1, selectin-E) and inflammation parameters (interleukin-1beta, interleukin-6) were measured. RESULTS: In the group of smokers, including both copper-smelters and control subjects, serum nitric oxide concentrations were lower than in non-smokers. In the serum of men occupationally exposed to lead, sICAM-1 concentrations were higher than in the control group. The lack of physiological correlation between serum concentration of nitric oxide and endothelin-1 resulted from interactions of tobacco smoking with lead exposure. CONCLUSIONS: Workers occupationally exposed to lead should be informed about adverse effects of tobacco smoking in terms of the interaction between nicotine and lead, two combined toxic agents affecting the circulatory system.

Adult↗

PubMed2002

Diet-induced mild hyperhomocysteinemia and increased salt intake diminish vascular endothelial function in a synergistic manner.

OBJECTIVES: We investigated the influence of hyperhomocysteinemia and high salt intake on sodium handling, oxidative state, vascular endothelial function and blood pressure in a rat model. METHODS: Eight-week-old male Sprague-Dawley rats were divided into subgroups and maintained for 4 weeks prior to experimentation on either control chow containing 0.36% methionine and 0.5% NaCl; or one of the following modified diets containing either 0.7% methionine, 8% NaCl or 0.7% methionine + 8% NaCl. Sodium handling, homocysteine metabolism, lipid profile, NO synthesis, oxidative state, blood pressure and relaxation to acetylcholine of carotid rings were evaluated and compared. RESULTS: Diet-induced mild hyperhomocysteinemia (plasma homocysteine levels 1.4-fold higher than control), by itself, had no significant influence on sodium excretion, vascular endothelial function and blood pressure. Increased salt intake had no influence on homocysteine metabolism, vascular endothelial function and blood pressure. The coexistence of mild hyperhomocysteinemia and high salt intake significantly diminished vascular endothelial function (rmax to acetylcholine; control chow 83.2 +/- 6.2%, 0.7% methionine diet 74.7 +/- 3.9%, 8% NaCl diet 85.1 +/- 4.6%, 0.7% methionine + 8% NaCl diet 57.9 +/- 6.6%) but manifested no rise in blood pressure. No significant difference in oxidative state was observed in this analysis. CONCLUSIONS: Diet-induced mild hyperhomocysteinemia, the extent of which is comparable with the levels that are associated with a predisposition to common atherosclerotic diseases, was found to induce vascular endothelial dysfunction only when accompanied by high salt intake.

Acetylcholine↗

PubMed1998

Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans.

BACKGROUND: Coronary endothelial dysfunction is characterized by an imbalance between endothelium-derived vasodilating and vasoconstricting factors and coronary vasoconstriction in response to the endothelium-dependent vasodilator acetylcholine. Thus, the present double-blind, randomized study was designed to test the hypothesis that long-term, 6-month supplementation of L-arginine, the precursor of the endothelium-derived vasodilator NO, reverses coronary endothelial dysfunction to acetylcholine in humans with nonobstructive coronary artery disease. METHODS AND RESULTS: Twenty-six patients without significant coronary artery disease on coronary angiography and intravascular ultrasound were blindly randomized to either oral L-arginine or placebo, 3 g TID. Endothelium-dependent coronary blood flow reserve to acetylcholine (10(-6) to 10(-4) mol/L) was assessed at baseline and after 6 months of therapy. There was no difference between the two study groups in clinical characteristics or in the coronary blood flow in the response to acetylcholine at baseline. After 6 months, the coronary blood flow in response to acetylcholine in the subjects who were taking L-arginine increased compared with the placebo group (149 +/- 20% versus 6 +/- 9%, P < 0.05). This was associated with a decrease in plasma endothelin concentrations and an improvement in patients' symptoms scores in the L-arginine treatment group compared with the placebo group. CONCLUSIONS: Long-term oral L-arginine supplementation for 6 months in humans improves coronary small-vessel endothelial function in association with a significant improvement in symptoms and a decrease in plasma endothelin concentrations. This study proposes a role for L-arginine as a therapeutic option for patients with coronary endothelial dysfunction and nonobstructive coronary artery disease.

Adult↗

PubMed2003

Plant sterols lower LDL cholesterol without improving endothelial function in prepubertal children with familial hypercholesterolaemia.

In adults with familial hypercholesterolaemia (FH), cholesterol lowering with statins has been shown to improve the endothelial function, a hallmark of early atherogenesis. Currently, therapeutic options for treating high cholesterol levels in FH children are limited. Plant sterols safely and effectively reduce serum cholesterol concentrations by inhibiting cholesterol absorption. Therefore, we evaluated the effect of plant sterols on cholesterol and vascular function in prepubertal children with FH. We included 41 children (5-12 years old) with FH in a double-blind crossover trial using spreads containing 2.3 g of plant sterols (mainly sitosterol and campesterol) per 15 g spread and a placebo spread for a 4-week period, separated by a 6-week washout period. Lipid levels and endothelial function were assessed after both 4-week treatment periods. Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery using a wall tracking system. Data were compared to those of 20 healthy controls. Intake of 2.3 g plant sterols per day decreased total cholesterol (-11%) and low-density cholesterol (-14%) as compared to placebo spread in FH children. FH children treated with placebo spread were characterized by an impaired FMD compared to healthy control children (7.2% +/- 3.4% versus 10.1% +/- 4.2%, p < 0.005). However, the reduction of LDL in FH children did not improve FMD (placebo: 7.2% +/- 3.4% versus plant sterols: 7.7% +/- 4.1%). In conclusion, the present study shows a clear reduction of LDL cholesterol by plant sterol treatment. However, short-term plant sterol treatment does not improve the endothelial function in FH children.

Brachial Artery↗

PubMed1997

Early pharmacologic intervention may prevent the deterioration in endothelial function after experimental myocardial infarction in rats: effects of ibopamine and captopril.

BACKGROUND: Endothelial function is progressively disturbed after myocardial infarction (MI), which may be related to both neurohumoral activation and hemodynamic alterations. Consequently, it may be suggested that drugs that favorably affect these factors may also have a positive effect on endothelial function. METHODS AND RESULTS: Rats underwent coronary ligation (n = 24) or remained unoperated (n = 21), and were randomized to captopril (25 mg/kg/d) or ibopamine (10 mg/kg/d) or remained untreated. Treatment was started following MI and lasted 8 weeks, after which rats were sacrificed for in vitro studies. Left ventricular end-systolic pressure was higher in rats treated with captopril (83 +/- 6 mmHg) and ibopamine (80 +/- 3 mmHg), as compared with untreated MI rats (48 +/- 6 mmHg, P < .01 for both). Increased plasma norepinephrine levels in MI rats were reduced by captopril and ibopamine (both P < .05). Infarct size was smaller in rats treated with captopril (26.7 +/- 3.6%, P < .05) and ibopamine (31.4 +/- 4.3%, P = NS), as compared with untreated rats (41.7 +/- 2.4%). Maximal endothelium-dependent relaxation (Emax; % precontraction) and the concentration of methacholine causing 50% Emax, expressed as negative log(pIC50) were significantly reduced in aortic rings from MI control subjects (pIC50 = 6.15 +/- 0.06 mol/L, Emax = 32.0 +/- 4.2%), as compared with normal control subjects (pIC50 = 6.57 +/- 0.07 mol/L, P < .001; Emax = 50.0 +/- 4.9%, P = .022). Captopril (pIC50 = 6.30 +/- 0.08 mol/L, Emax = 45.1 +/- 7.0%) and ibopamine (pIC50 = 6.60 +/- 0.08 mol/L, Emax = 43.8 +/- 5.2%) improved these parameters in MI rats. CONCLUSION: The results demonstrate preservation of endothelial function by early pharmacologic intervention after experimental MI in rats in the setting of concomitant reduction in infarct size.

Animals↗

PubMedDate not supplied

Interactions between autonomic nervous system activity and endothelial function: a model for the development of cardiovascular disease.

OBJECTIVES: Endothelial dysfunction is a new pathway in cardiovascular disease (CVD) development. Psychosocial factors have been little studied in relation to endothelial function, although they may interact via associations with the autonomic nervous system (ANS). The purpose of this review is to propose a model by which psychosocial factors are related to CVD development through interactions between the ANS and vascular endothelium. METHODS: The literature supporting an interaction between the ANS and endothelium in healthy and disease states is reviewed. Potential mechanisms linking the two systems are explored as a pathway for CVD development. RESULTS: Endothelial dysfunction and impaired cardiovascular ANS regulation are both markers for increased CVD risk. Sympathetic nerves and vascular endothelial cells share a functional antagonism in healthy states to maintain appropriate blood vessel tone. Alterations in sympathetic activity and endothelial cell function are both observed early in the development of CVD and may result from an inability to maintain the functional antagonism. Impairments in either ANS regulation or endothelial function may contribute to further disease development by evoking maladaptive changes in the opposing system. CONCLUSIONS: Although interactions between cardiovascular ANS regulation and endothelial function are likely involved in CVD development, further research is needed to determine whether ANS and endothelium interactions are a plausible pathway linking psychosocial factors with increased CVD risk.

Adult↗

PubMed1998

Effects of candesartan cilexetil and enalapril on structural alterations and endothelial function in small resistance arteries of spontaneously hypertensive rats.

It was previously observed that a significant regression of structural alterations and endothelial dysfunction in mesenteric small arteries of spontaneously hypertensive rats (SHRs) may be obtained after therapy with angiotensin-converting enzyme (ACE) inhibitors. It is not clear whether angiotensin II-type 1 receptor blockers may share this properties. We evaluated the effects of the ACE inhibitor enalapril and of the angiotensin II-receptor blocker candesartan cilexetil on structural alterations of mesenteric small resistance arteries, on cardiac mass, and on endothelial function in SHRs. Seventy-three rats were included in the study. Sixteen SHRs were treated with enalapril and 21 with candesartan cilexetil, whereas 18 Wistar-Kyoto (WKY) and 18 SHRs were untreated. Enalapril and candesartan cilexetil were administered in the drinking water from weeks 4 to 12 of age. Blood pressure was measured noninvasively every week. The rats were killed at the end of the treatment period, after 3 or 4 days of therapeutic washout. Heart weight/body weight ratio (HW/BW) was measured. Mesenteric arterioles were dissected and mounted on a micromyograph (Mulvany's technique). Then the media-to-lumen ratio (M/L) was evaluated. In addition, endothelium-dependent and endothelium-independent relaxation was evaluated by dose-response curves to acetylcholine (in the presence or absence of a bradykinin-receptor blocker and of indomethacin) and sodium nitroprusside. Systolic blood pressure was significantly reduced by both drugs, compared with untreated SHRs, although the hypotensive effect was greater with enalapril than with candesartan cilexetil. A significant reduction of M/L of mesenteric small arteries and of HW/BW was observed in SHRs treated with candesartan cilexetil or enalapril. A significant improvement of endothelial function, as evaluated by a dose-response to acetylcholine, was observed. The acetylcholine-induced vasodilatation was similar after addition to the organ bath of a selective blocker of bradykinin receptors, thus suggesting a minor role (if any) of the increased local availability of bradykinin, as a consequence of inhibition of ACE, in the improvement of endothelial function observed after enalapril treatment. In addition to a satisfactory antihypertensive effect observed with both drugs, candesartan cilexetil and enalapril were proven to be equally effective in reducing structural alterations in mesenteric small resistance arteries, in normalizing cardiac mass, and in improving endothelial function. The inhibition of bradykinin breakdown does not seem to be involved in the improvement of endothelial dysfunction observed with ACE inhibitors.

Acetylcholine↗

PubMed2005

Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk.

OBJECTIVE: Erectile dysfunction (ED) is often associated with a cluster of risk factors for coronary artery disease and reduced endothelial function. Acute and chronic administration of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, improves endothelial function in patients with ED. Tadalafil (TAD) is a new PDE5 inhibitor with a long half life that allows alternate day administration. Aim of the study was to evaluate whether chronic therapy (4 weeks) with TAD improves endothelial function in patients with increased cardiovascular risk and whether this effect is sustained after discontinuation of therapy. METHODS: We randomized 32 patients with increased cardiovascular risk to receive either TAD 20 mg on alternate days or matching placebo (PLB) for 4 weeks. Patients underwent evaluation of brachial artery flow-mediated dilation (FMD), nitrite/nitrate and endothelin-1 plasma levels at baseline, at the end of treatment period and after two-weeks follow-up. RESULTS: At 4 weeks, FMD was significantly improved by TAD (from 4.2+/-3.2 to 9.3+/-3.7%, p<0.01 vs. baseline), but was not modified by PLB (from 4.1+/-2.8 to 4.0+/-3.4%, p=NS). At 6 weeks the benefit in FMD was sustained in patients that received TAD (9.1+/-3.9% vs. 4.2+/-3.2%, p=0.01 vs. baseline; 9.1+/-3.9% vs. 9.3+/-3.7%, vs. 4 weeks, p=NS) while no changes in FMD were observed in patients randomized to PLB. Also, compared to baseline, a net increase in nitrite/nitrate levels (38.2+/-12.3 vs. 52.6+/-11.7 and 51.1+/-3.1, p<0.05) and a decrease in endothelin-1 levels (3.3+/-0.9 vs. 2.9.+/-0.7 and 2.9+/-0.9, p<0.05) was found both at four and six-weeks after TAD; these changes were inversely correlated as shown by regression analysis (adjusted R2=0.81, p<0.0001). CONCLUSIONS: Chronic therapy with TAD improves endothelial function in patients with increased cardiovascular risk regardless their degree of ED. The benefit of this therapy is sustained for at least two weeks after the discontinuation of therapy. Larger studies are needed in order to assess the possible clinical implications of chronic therapy with TAD.

Aged↗

PubMed2003

Effects of alcohol intake on endothelial function in men: a randomized controlled trial.

BACKGROUND: Regular light consumption of alcohol appears to reduce the risk of cardiovascular disease, whereas in heavier drinkers the opposite effect is seen. This biphasic relationship could partly be due to contrasting actions of low and high alcohol intake on endothelial function. OBJECTIVE: To determine whether reducing alcohol intake in moderate-to-heavy drinkers (40-110 g/day) would improve conduit artery endothelial function as assessed by post-ischaemic brachial artery flow-mediated dilatation (FMD). METHODS: In a two-way cross-over study, 16 healthy men either substituted their usual alcohol intake with a 0.9% alcohol beer or maintained their usual alcohol intake during sequential 4-week periods. At the end of each period of FMD and glyceryl trinitrate-induced brachial artery dilatation, blood pressure, plasma lipids, homocysteine and biomarkers of alcohol consumption (gamma-glutamyl transpeptidase) and endothelial function (E-selectin, von Willebrand factor, endothelin-1) were assessed. RESULTS: The participants reduced their alcohol intake from 72.4 to 7.9 g/day. This self-reported reduction in alcohol intake was corroborated by significant decreases in gamma-glutamyl transpeptidase (24%). The decrease in alcohol intake resulted in reductions in total cholesterol (5%), high-density lipoprotein cholesterol (17%), homocysteine (9%) and systolic and diastolic blood pressure [5 mmHg (P = 0.01) and 4 mmHg (P = 0.003), respectively]. There was no effect of alcohol on FMD (6.23 +/- 0.75% compared with 6.24 +/- 0.71%, P = NS), glyceryl trinitrate-induced vasodilatation, E-selectin, endothelin-1 and von Willebrand factor. CONCLUSION: Substantial reduction in alcohol intake in healthy moderate-to-heavy drinkers does not improve endothelial function as measured by post-ischaemic flow-mediated dilatation of the brachial artery or biomarkers of endothelial function.

Adult↗

PubMed1997

Association of gestational diabetes with abnormal maternal vascular endothelial function.

OBJECTIVE: To evaluate vascular endothelial function in isolated small arteries from women with gestational diabetes. METHODS: Small subcutaneous arteries (mean luminal diameter approximately 250 microns) were dissected from biopsies obtained at caesarean section in 14 normotensive women with gestational diabetes and in 18 normotensive nondiabetic pregnant women. Vascular function was determined after mounting the arteries on a small vessel myograph. RESULTS: Pre-constricted arteries from gestational diabetic pregnant women demonstrated poor relaxation to acetylcholine, an endothelium-dependent vasodilator (pEC50, mean [SE], 6.98 [0.10] vs normal pregnant, 7.28 [0.08], P < 0.03; % maximum relaxation, median [range], 88.2 [42.4-99.4] vs normal pregnant 94.2 [71.8-100.0], P < 0.01). In the presence of indomethacin relaxation to acetylcholine was similar in both groups suggesting a deficiency in dilator prostaglandin synthesis in the arteries from the diabetic women. The nitric oxide synthase inhibitor NG-monomethyl-L-arginine further reduced sensitivity of arteries to acetylcholine but to a similar degree in both normal pregnant and gestational diabetic women. Relaxation to sodium nitroprusside, an indicator of sensitivity of the vascular smooth muscle to nitric oxide, was similar in both groups. CONCLUSIONS: Maternal vascular endothelial dysfunction may contribute to the increased incidence of cardiovascular disorders in women with gestational diabetes.

Acetylcholine↗

PubMed2004

Assessing the prognostic value of coronary endothelial function in patients referred for a first coronary angiogram.

At present, the value of endothelial function as a prognostic tool has been evaluated only in selected groups of patients with mild or minor coronary artery disease, not in the complete spectrum of patients presenting with angina. The objective of this study was to evaluate whether endothelium-dependent vasodilation of the coronary arteries in response to acetylcholine infusion as a marker of endothelial function would have prognostic value in patients referred for a first coronary angiogram. The data suggest that endothelial function assessment does not contribute to the prediction of outcomes in patients referred for a first coronary angiogram.

Adolescent↗

PubMed2002

Insulin resistance and vessel endothelial function.

IRS is a complex disease consisting of a clustering of metabolic disorders, of which hyperglycaemia, hyper-insulinaemia and dyslipidaemia are the most important. Endothelial dysfunction plays an important role in the pathogenesis of atherosclerosis. The effects of hyperinsulinaemia seem to depend on lipidaemia and glycaemia. Hyperglycaemia and hyperlipidaemia have detrimental effects on endothelial function in the fasting as well as the postprandial states. In both situations, the generation of ROS and vasoactive molecules plays a major role in interfering with the atheroprotective endothelium-dependent NO system. Treatment of IRS in regard to endothelial function should be focused initially on lifestyle improvement, such as stopping smoking and eating a balanced diet containing antioxidant vitamins, folic-acid, L-arginine and long-chain omega-3 unsaturated FA. Strict glucose control has shown to improve endothelial function and decrease microvascular complications. However, macrovascular complications, in line with endothelial functional improvement, have so far been reduced only when treatment was focused on other characteristics of the IRS syndrome, in particular dyslipidaemia. Other relevant treatments include ACE inhibitors and thiazolidinediones, and probably tetrahydrobiopterin and folic acid supplementation. Future studies should address the effects of therapeutic neovascularization on endothelial dysfunction.

Endothelium, Vascular↗

PubMed2005

Antiatherosclerotic effects of dietary supplementations of garlic and turmeric: Restoration of endothelial function in rats.

Protections of endothelial integrity by elimination of certain risk have proven to be effective in maintaining hemostasis and in slowing the progress of the cardiovascular disease. Indigenous drugs are the natural source of protection against these disorders, which can be used more effectively by the knowledge of their active ingredients as well as by their mechanism of action. Most prominent among these drugs are garlic, [Alium sativum L., Family: Liliaceae, Bulbs] and turmeric [Curcuma longa L., Family: Zingiberaceae, Rhizomes]; commonly used Indian traditional spices. In the present study, we examined the atheroscleroprotective potential of diet supplementation of garlic and turmeric by measuring serum lipid profile, changes in cardiovascular parameters i.e. arterial blood pressure, electrocardiogram and heart rate. We further tried to elucidate the mechanism of restoration of endothelial function and the role of endothelium-derived factors mainly, nitric oxide (NO) and cycloxygenase derived contracting factors. A notable restoration of arterial blood pressure was seen in animals on garlic and turmeric supplemented diet. Animals on supplemented diet showed a significantly enhanced vasorelaxant response to adenosine, acetylcholine, isoproterenol and contractile effect of 5-hyderoxytryptamine was significantly attenuated. Inhibition of these responses by L-NMMA was smaller in tissues from herbal treated animals. Incubation of tissues with L-arginine (10(-5) M) resulted in a significant reversal of L-NMMA induced inhibition of endothelium-mediated relaxation, which appeared to be pronounced in rings from animals supplemented with herbs as compared to hypercholesterolemic animals. Addition of indomethacin (10(-5) M) augmented the relaxation in all the groups of animals. The present study demonstrated that garlic and turmeric are potent vasorelaxants as well as reduce the atherogenic properties of cholesterol. Whether combination of these vasodilators in cardiovascular disorders with increased peripheral vascular resistance remains to be determined.

Animals↗

PubMed1999

Coronary endothelial function is preserved with chronic endothelin receptor antagonism in experimental hypercholesterolemia in vitro.

Hypercholesterolemia is associated with increased circulating and tissue endothelin-1 immunoreactivity, decreased nitric oxide (NO) activity, and altered endothelial function. We tested the hypothesis that chronic endothelin receptor antagonism preserves endothelial function and increases NO in experimental porcine hypercholesterolemia. Pigs were randomized to 3 groups: Group 1, a 2% high-cholesterol (HC) diet alone (n=7); group 2, RO-48-5695, a combined endothelin receptor antagonist, and an HC diet (n=8); and group 3, ABT-627, a selective endothelin-A receptor antagonist, and an HC diet (n=8). Coronary epicardial and arteriolar endothelial function was determined by a dose-response relaxation to bradykinin (10(-11) to 10(-6) mol/L), in all groups and in pigs maintained on a normal diet. Plasma total oxidized products of NO (NO(x)) were determined by chemiluminescence at baseline and after 12 weeks. Bradykinin-stimulated coronary epicardial and arteriolar relaxation in group 1 was attenuated compared with normal-diet controls. This relaxation was normalized with endothelin receptor antagonism. Plasma NO(x) decreased after 12 weeks in group 1 (-74.8+/-5.5%). This decrease was attenuated in the endothelin receptor antagonist groups (group 2, -28.2+/-15.0%; group 3, -38.9+/-20.6%). Chronic endothelin receptor antagonism preserves coronary endothelial function and increases NO in hypercholesterolemia. This study supports a role of endothelin-1 in the regulation of NO activity and suggests a possible therapeutic role for endothelin receptor antagonists in hypercholesterolemia.

Animals↗

PubMed2000

Cholesterol lowering with pravastatin improves resistance artery endothelial function: report of six subjects with normal coronary arteriograms.

STUDY OBJECTIVES: Improvement in coronary artery endothelial function has been demonstrated after cholesterol lowering in hypercholesterolemic patients with significant atherosclerosis. However, to our knowledge, no previous study has shown improvement in resistance artery function in subjects with normal coronary arteries after cholesterol lowering. The purpose of our study was to investigate the effect of cholesterol lowering with pravastatin on coronary resistance artery endothelial function in the setting of angiographically normal coronary arteries. METHODS: Invasive testing of coronary endothelial and vasomotor function was performed at baseline and after 6 months of pravastatin treatment in six patients with normal coronary arteriograms. RESULTS: After 6 months of pravastatin treatment, low-density lipoprotein cholesterol level dropped from 157+/-11 to 117+/-8 mg/dL (p = 0.02) and percent increase in coronary blood flow after acetylcholine improved from 97+/-13% to 160+/-16% (p = 0.01). There was a trend (p = 0.17) toward enhanced epicardial dilation in response to acetylcholine after pravastatin treatment when compared with the baseline study. CONCLUSIONS: Our study demonstrates significant improvement in coronary resistance artery endothelial function after 6 months of cholesterol lowering with pravastatin in six subjects presenting with chest pain who were found to have normal coronary arteriograms. A trend toward improved epicardial vasomotion was also observed.

Adult↗

PubMed1994

Assessment of endothelial function during oral contraception in women with insulin-dependent diabetes mellitus.

The effects of contraceptive steroids on the expression of endothelial homeostasis were examined by direct and indirect measures in women with insulin-dependent diabetes mellitus (IDDM) in a prospective nonrandomized controlled study. Study subjects were 13 women with uncomplicated IDDM treated with a monophasic combination of 30 micrograms ethinyl estradiol and 75 micrograms gestodene for 12 consecutive cycles and 13 women of comparable diabetic status as control. During the study period, none of the participants developed increased renal albumin excretion, which was used as a direct measure of endothelial function. In the indirect assessment of endothelial function, we found a proportionate increase in plasma levels of thrombin-antithrombin III (TAT) complexes and D-dimer during treatment. Hormonal intake was followed by decreased antigen concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (type 1 [PAI-1]), whereas the activities of t-PA and PAI-1 were unchanged. Plasma levels of plasminogen and histidine-rich glycoprotein (HRG) increased and decreased, respectively, whereas an increase in von Willebrand factor was observed in the treatment group. No significant changes in direct or indirect measures were observed in the control group during the observation period of 12 months. In conclusion, no adverse effect on endothelial function was demonstrated by direct measures, but our findings suggest that a procoagulant state, compensated by enhanced activity of the fibrinolytic system, is induced by hormonal treatment. Clinical and metabolic monitoring is recommended if the use of oral contraceptives in women with IDDM is extended.

Adult↗

PubMed1998

Glyc-oxidized LDL impair endothelial function more potently than oxidized LDL: role of enhanced oxidative stress.

Hypercholesterolemia is associated with impairment of endothelial function due to increased levels of LDL. In diabetic patients, however, attenuation of endothelial function occurs even under normocholesterolemic conditions. Here we assessed whether glycation of LDL potentiates their influence on endothelial function, with particular emphasis on the oxidizability of LDL and the role of O2-. Human LDL was glycated by dialyzation for 7 days against buffer containing 200 mmol/l glucose, or sham-treated without glucose, and oxidized by incubation with Cu2+. Glycation significantly enhanced the oxidizability of LDL, as detected by diene formation and by electrophoretic mobility (27.5 mm for oxidized LDL vs. 34 mm for oxidized glycated LDL at 20 h of oxidation). Isolated rings of rabbit aorta were superfused with physiological salt solution, and isometric tension was recorded. Incubation of the aortic rings with sham-treated or with glycated LDL, not oxidized, had no influence on acetylcholine-induced, endothelium-dependent relaxation. Exposure of the aortic rings to oxidized non-glycated LDL caused a significant inhibition (30% at 1 microM acetylcholine) of the endothelium-dependent relaxation only in the presence of diethyl-dithiocarbamate (DDC), an inhibitor of the endogenous superoxide dismutase (SOD). Incubation of aortic rings with oxidized glycated LDL attenuated endothelium-dependent relaxation even in the absence of DDC (by 31% at 1 microM acetylcholine). The presence of DDC potentiated the inhibition of relaxation (65% inhibition at 1 microM acetylcholine), and co-incubation with exogenous SOD and catalase prevented the inhibition of relaxation, indicating a mediator role of O2-. Endothelium-independent relaxation induced by forskolin was unaffected by any of the lipoproteins. Using a chemiluminescence assay, significantly increased O2- production of aortic rings pretreated with oxidized glycated LDL (4101 +/- 360 counts/s) in comparison to control rings (753 +/- 81 counts/s) or arteries pretreated with oxidized non-glycated LDL (2358 +/- 169 counts/s) could be detected, suggesting that enhanced NO-inactivation by O2- could be the underlying mechanism for the stronger impairment of endothelium-dependent dilations by oxidized glycated LDL. Glycation increases the oxidizability of LDL and potentiates its endothelium-damaging influence. The likely mechanism for attenuation of endothelium-dependent dilations is increased formation of O2-, resulting in inactivation of nitric oxide. This mechanism may play an important role in diabetic patients and may contribute to disturbed organ perfusion.

Animals↗