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PubMed1997

Aerobic exercise capacity remains normal despite impaired endothelial function in the micro- and macrocirculation of physically active IDDM patients.

The aim of the present study was to examine if diabetes in the absence of neuropathy affects the exercising capacity of IDDM patients, and whether regular, intense training has a beneficial effect on endothelial function. Five groups of subjects were studied: 23 healthy control subjects who exercised regularly (age 33 +/- 6 years), 23 nonneuropathic type 1 diabetic patients who exercised regularly (age 33 +/- 6 years, IDDM duration 11 +/- 8 years), 7 neuropathic type 1 diabetic patients who exercised regularly (age 36 +/- 7 years, IDDM duration 22 +/- 8 years), 18 healthy subjects who did not exercise regularly (age 34 +/- 7 years), and 5 nonneuropathic type 1 diabetic patients who did not exercise regularly (age 31 +/- 4 years, IDDM duration 20 +/- 3 years). All groups were matched for age, sex, and body weight. No differences existed in the energy expenditure per week in physical activity among the three exercising groups or between the two nonexercising groups. The maximal oxygen uptake was similar between control and diabetic nonneuropathic exercisers, and among diabetic neuropathic exercisers, control nonexercisers, and diabetic nonexercisers; however, a significant difference existed between the first two and the last three groups (P < 0.0001). A stepwise increase was found in the resting heart rate among the groups, ranging from the lowest in control exercisers to the highest in diabetic nonexercisers, but the maximal heart rate was lower only in diabetic neuropathic exercisers compared with all other groups (P < 0.05). Assessments of endothelial function in both macro- and microcirculation were performed in 12 control exercisers, 10 diabetic nonneuropathic exercisers, 5 diabetic neuropathic exercisers, 17 control nonexercisers, and 4 diabetic nonexercisers. When all diabetic patients were considered as one group and all control subjects as another, the microcirculation endothelial function in the diabetic group was reduced compared with the control subjects (91 +/- 49 vs. 122 +/- 41% flux increase over baseline; P < 0.05). In contrast, no differences existed among the three diabetic groups or between the two control groups. Similarly, in macrocirculation, a reduced response during reactive hyperemia was observed in the diabetic patients compared with control subjects (7.0 +/- 4.5 vs. 11.2 +/- 6.6% diameter increase; P < 0.05), whereas again no difference existed among the three diabetic groups or between the two control groups. These data suggest that diabetes per se does not affect aerobic exercise capacity (VO2max) in physically active individuals, but is reduced in the presence of neuropathy. In addition, regular exercise training involving the lower extremities does not improve the endothelial function in the micro- and macrocirculation of the nonexercised upper extremity in type 1 diabetic patients.

Adult↗

PubMed2006

The endothelial function in cardiac surgery.

Cardiac operations with cardiopulmonary bypass exerts many different actions which modify the natural function of endothelial cells. The main determinant is the activation of the coagulation system both through the intrinsic and extrinsic pathways, leading to an overwhelming thrombin formation. To counteract the coagulant effects of thrombin, heparin is used in large doses. As a result, the endothelium is asked to promote all its anticoagulant properties, basically through the AT release from the surface, the tissue factor pathway inhibitor release, and the activation of the protein C protein S system. At the end of cardiac operations, all these systems are depleted, and low levels of antithrombin, tissue factor pathway inhibitor, protein C are available for further anticoagulant effects. There is the evidence that levels of antithrombin activity below 50% at the end of cardiac operations with cardiopulmonary bypass are associated to bad outcomes in terms of surgical revision rate, thromboembolic events, and neurological events. Exogenous antithrombin administration has a well defined action in limiting thrombin formation during cardiac operations; however, we are still lacking an evidence-based information about the clinical impact of this and others possible preventive strategies based on exogenous administration of antithrombin before or during cardiac operations.

Cardiac Surgical Procedures↗

PubMed2005

Effects of rosuvastatin on endothelial function in patients with familial combined hyperlipidaemia (FCH).

OBJECTIVE: Although several studies have reported a positive effect of statins on endothelial vasoreactivity, most studies performed in subjects with type 2 diabetes mellitus report no effect at all. This lack of effect may be related to the existence of insulin resistance, or to insufficient lowering of atherogenic (apo)lipoproteins. Therefore, we tested in this study whether treatment of insulin resistant familial combined hyperlipidaemia (FCH) patients with a high dose (40 mg/day) of the potent rosuvastatin was able to improve endothelial function, without necessarily improving insulin sensitivity. RESEARCH DESIGN AND METHODS: In a double-blind randomised crossover study, 18 subjects with FCH (without evident cardiovascular disease, mean [standard deviation] age 54 [7] years) underwent a 4-week run-in period after which they were randomised to treatment with placebo once daily for 12 weeks, followed by rosuvastatin 40 mg/day for 12 weeks or vice versa. Endothelial function was determined after 8 and 12 weeks of both treatment periods, respectively, by measurement of flow-mediated vasodilation (FMD) using high-resolution ultrasound and by measurement of vasodilator response to intrabrachial acetylcholine (Ach) by venous occlusion plethysmography (forearm blood flow [FBF]). RESULTS: Plasma levels of lipids, (apo)lipoproteins and high-sensitivity C-reactive protein (hsCRP) improved significantly after rosuvastatin therapy compared to placebo. However, rosuvastatin had no effect on homeostasis model assessment (HOMA)-indices or on vasodilator responses to intra-brachial acetylcholine-infusion (FBF-ratio increased from a mean of 1.28 [SD: 0.46] to 5.82 [3.44] after rosuvastatin and from 1.33 [0.67] to 5.99 [3.89] after placebo, p = 0.35). Endothelium-dependent FMD was also unchanged (1.6% [3.1%] vs. 3.2% [3.5]%, p = 0.56 rosuvastatin vs. placebo, respectively). CONCLUSION: In patients with FCH, a 12-week treatment of rosuvastatin 40 mg/day did not improve endothelial function (either in large conduit vessels or in resistance vessels), despite significant improvements in plasma lipids, (apo)lipoproteins. and low-grade inflammation.

Adult↗

PubMed2005

Endothelial function in healthy 11-year-old children after dietary intervention with onset in infancy: the Special Turku Coronary Risk Factor Intervention Project for children (STRIP).

BACKGROUND: Early childhood introduction of nutritional habits aimed at atherosclerosis prevention reduces children's serum total cholesterol concentration, but its effect on vascular endothelial function is unknown. METHODS AND RESULTS: Between 1990 and 1992, we randomized healthy 7-month-old infants (n=1062) to intervention (low-saturated-fat diet) and control (unrestricted diet) groups. At the age of 11 years, endothelium-dependent (flow-mediated) and endothelium-independent (nitrate-mediated) vasodilatory responses of the brachial artery were measured with high-resolution ultrasound in 179 intervention and 190 control children. The effect of intervention on endothelial function was significant in boys (P=0.0034) but not in girls (P=0.69). The maximum endothelium-dependent dilation response (mean+/-SD) was 9.62+/-3.53% and 8.36+/-3.85% in intervention boys and control boys and 8.84+/-4.00% and 8.44+/-3.60% in intervention girls and control girls, respectively. Intervention had no effect on nitrate-mediated dilation. The difference in endothelial function in boys remained significant after adjustment for current serum total or LDL cholesterol but became nonsignificant after adjustment for mean cholesterol measured under 3 years of age (adjusted means: 9.46% [CI 8.68% to 10.24%] versus 8.54% [CI 7.75% to 9.32%], P=0.11). CONCLUSIONS: A low-saturated-fat diet introduced in infancy and maintained during the first decade of life is associated with enhanced endothelial function in boys. The effect is explained in part by the diet-induced reduction in serum cholesterol concentration.

Atherosclerosis↗

PubMed2005

Augmentation of endothelial function following exercise training is associated with increased L-arginine transport in human heart failure.

We have reported previously a decrease in the clearance of the NO (nitric oxide) precursor L-arginine in the forearm circulation of CHF (congestive heart failure) patients, suggesting a potential rate-limiting mechanism contributing to the common finding of endothelial dysfunction in CHF. Given data that show exercise training augments endothelial function in CHF, the aim of the present study was to investigate whether these improvements were due to an increase in L-arginine transport. Measures of L-arginine transport, endothelial function and exercise capacity were repeated before and after 8 weeks of "usual living" or exercise training in 21 CHF patients [NYHA (New York Heart Association) class II/III]. Exercise capacity (6-min walk test) increased following exercise training (496+/-21 to 561+/-17 m; P=0.005), whereas the control group demonstrated no change [488+/-18 to 484+/-21 m; P=ns (not significant)]. Basal FBF (forearm blood flow) remained stable following exercise training (2.68+/-0.55 to 2.46+/-0.32 ml.min(-1).100 ml(-1) of tissue) and "usual living" (2.16+/-0.37 to 2.91+/-0.55 min(-1).100 ml(-1) of tissue). FBF responses to ACh (acetylcholine) increased following exercise by 49.6+/-17.7% (area under curve; P=0.01) demonstrating augmented endothelial function. FBF responses to SNP (sodium nitroprusside) were also improved following exercise training (30.8+/-8.2%; P=0.02). There was no change in vascular function in the "usual living" group. The clearance of L-arginine was significantly increased following involvement in the exercise programme (69.4+/-7.8 to 101.0+/-9.5 ml/min; P=0.04), whereas there was no change in the "usual living" group (78.4+/-17.5 to 81.0+/-14.9 ml/min; P=ns). In conclusion, the augmentation in endothelial function observed following exercise may be due, in part, to an increase in the transport of L-arginine in CHF patients.

Acetylcholine↗

PubMed2004

Comparison of the effects of omapatrilat and irbesartan/hydrochlorothiazide on endothelial function and cardiac hypertrophy in the stroke-prone spontaneously hypertensive rat: sex differences.

OBJECTIVE: The novel antihypertensive agent, omapatrilat, is both an inhibitor of neutral endopeptidase and angiotensin-converting enzyme. This study investigated the effects of omapatrilat in comparison with an angiotensin I-receptor antagonist/diuretic combination on blood pressure, endothelial function and cardiac hypertrophy in stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: Male and female SHRSP were treated orally with omapatrilat or irbesartan plus hydrochlorothiazide (I + H) or vehicle for 8 weeks. Systolic blood pressure was measured weekly by tail-cuff. Cardiac hypertrophy was monitored by echocardiography at 8, 12 and 16 weeks of age. Endothelial function [basal nitric oxide (NO) bioavailability and stimulated NO release] was examined in carotid arteries using organ bath pharmacology and in mesenteric resistance arteries using wire myography. RESULTS: Compared with untreated controls, omapatrilat and I + H significantly attenuated hypertension [male control, 198.3 +/- 6.9 mmHg versus omapatrilat, 149.6 +/- 3.8 mmHg (F = 8.63 P < 0.0001), versus I + H, 145.6 +/- 5.1 mmHg (F = 7.38 P < 0.0001); female control, 170.3 +/-8.3 mmHg versus omapatrilat, 120.0 +/- 4.6 mmHg (F = 8.36, P < 0.0001), versus I + H, 112.2 +/- 2.9 mmHg (F = 9.08, P < 0.0001)] and left ventricular hypertrophy [male + female controls, 3.02 +/- 0.38 mg/g versus omapatrilat, 2.47 +/- 0.26 mg/g (P < 0.0001; 95% confidence interval, 0.27, 0.83), versus I + H, 2.49 +/- 0.21 mg/g (P < 0.0001; 95% confidence interval, 0.25, 0.83)]. Both treatments also significantly increased male carotid artery basal NO bioavailability relative to control [control, 0.62 +/- 0.17 g/g versus omapatrilat, 1.95 +/- 0.17 g/g (P < 0.0001; 95% confidence interval, -1.83, -0.36), versus I + H, 1.57 +/- 0.21 g/g (P < 0.026; 95% confidence interval, -1.31, -0.12)]. However, stimulated NO (EC50) was only improved in omapatrilat-treated males [controls, 0.19 +/- 0.06 micromol/l versus omapatrilat, 0.05 +/- 0.01 micromol/l (P = 0.05; 95% confidence interval, -1.16, -0.03)]. CONCLUSIONS: Omapatrilat treatment significantly reduced left ventricular hypertrophy and improved endothelial function in carotid arteries from male SHRSP by NO-dependent mechanisms. Despite equivalent antihypertensive and antihypertrophic actions, a similar improvement in endothelial function, specifically stimulated NO release, was not observed after treatment with I + H.

Animals↗

PubMed2005

[A study on endothelial function and inflammation factors in the first degree relatives of type 2 diabetics with normal glucose tolerance].

OBJECTIVE: To study the vascular endothelial function and the level of inflammation factors in the first degree relatives (FDR) of type 2 diabetes (T2DM) patients with normal glucose tolerance and related factors. METHODS: Vascular endothelial function, plasma plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1) and insulin active index (IAI) were measured in 57 FDR and 31 controls. RESULTS: As compared with the controls, there were less endothelium-dependent vasodilation [(12.45 +/- 3.37)% vs (5.03 +/- 0.34)%] and IAI [(-3.79 +/- 0.57) vs (-4.11 +/- 0.46)], higher PAI-1 [(30.46 +/- 12.28) microg/L vs (39.25 +/- 6.54) microg/L] and higher VCAM-1 [(637.31 +/- 107.32) microg/L vs (742.39 +/- 124.31) microg/L] in the FDR (P < 0.05). CONCLUSION: There were decreased IAI, damaged endothelial function and impaired fibrinolysis in the first degree relatives of T2DM patients with normal glucose tolerance.

Adult↗

PubMed1997

Coronary endothelial function in open heart surgery.

1. During open heart surgery, the heart is arrested and protected by hyperkalaemic cardioplegia. The coronary endothelium may be damaged by ischaemia-reperfusion and cardioplegia. Subsequently, this may affect cardiac function immediately after cardiac surgery and cause mortality or morbidity. 2. Our studies have investigated coronary endothelial function after exposure to hyperkalaemia (K+ 20 or 50 mmol/L). Endothelium-dependent relaxation and hyperpolarization of the coronary smooth muscle and intracellular free calcium concentration in the endothelial cell were measured with regard to K+ exposure. 3. Endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation to A23187, bradykinin, and substance P in the presence of either U46619 (10 nmol/L)- or K+ (25 mmol/L)-induced contraction was reduced after exposure to either 20 or 50 mmol/L K+. 4. The hyperpolarization of the membrane potential in response to the endothelium-derived relaxing factor (EDRF) stimuli was also reduced by exposure to K+. 5. The intracellular free calcium concentration remained unchanged after exposure to hyperkalaemia. 6. We conclude that the EDHF-mediated coronary endothelial function is impaired after exposure to hyperkalaemic cardioplegia. The impairment of this function is due to the changed effect of EDHF on the smooth muscle cell, probably through partially depolarizing the membrane and affecting K+ channels rather than alteration of its biosynthesis/release in the endothelial cell. It may be of use to search for a new cardioplegia that preserves this endothelial function during open heart surgery.

Animals↗

PubMed2005

Early and late effects of alcohol ingestion on blood pressure and endothelial function.

Previous investigations have shown a biphasic effect of alcohol on blood pressure (BP). However, there are no studies on possible simultaneous influences in endothelial function. This study aims to evaluate the early and late effects of alcohol ingestion on vascular and endothelial function parameters in healthy young men. The diameter of brachial artery (DBA), endothelium-dependent flow-mediated dilatation, endothelium-independent nitroglycerin-mediated dilatation, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate were measured 30 min before intake, 4 h after intervention (when there is a reported hypotensive effect of alcohol), and after 13 h (subsequent increase in BP). The study group consisted of 100 males aged 18-25 years who were evaluated by brachial artery ultrasound. Subjects were randomized to drink either an alcoholic (60 g of ethanol) or a similar nonalcoholic beverage. Alcohol induced a biphasic effect on SBP and DBP, with a 4-h decrease followed by an increase after 13 h. After 4 h, the alcohol-drinking group presented a DBA increase that was significant at baseline and after hyperemia but not after nitroglycerin administration. There were no DBA differences between the intervention and control groups 13 h after drinking. This study replicates the initial reports of alcohol-induced biphasic alteration in BP. Our results showed that despite the late increase in BP, there were no accompanying changes in endothelial function.

Adolescent↗

PubMed1999

Abnormalities of vascular endothelial function may contribute to increased coronary heart disease risk in UK Indian Asians.

OBJECTIVE: To test the hypothesis that abnormalities of endothelial function are present in Indian Asians and may contribute to their increased coronary heart disease risk. SETTING: Single centre in west London. PATIENTS: 26 Indian Asian and 18 European white healthy male subjects, aged 35 to 61 years recruited from general practice lists. DESIGN: Brachial artery diameter responses to reactive hyperaemia and sublingual glyceryl trinitrate were compared using high resolution ultrasound. RESULTS: Mean (SEM) flow mediated, endothelium dependent dilatation was reduced in Indian Asians compared with European whites, at 3.2 (0.8)% v 5.9 (1.0)%, p = 0.03. In contrast, there were no significant differences in baseline brachial arterial diameter (4.6 (0.1) v 4.6 (0.1) mm, p = 0.65) or glyceryl trinitrate induced dilatation (18.8 (1.5)% v 18.5 (1.7)%, p = 0.90) between Indian Asians and European whites, respectively. Univariate analysis showed that Indian Asian race was significantly associated with impaired flow mediated dilatation (regression coefficient = -2.8 (1.3)%, p = 0.03), and in multivariate analysis, this relation was independent of both conventional coronary heart disease risk factors and markers of insulin resistance. CONCLUSIONS: Endothelial function is impaired in healthy UK Indian Asians compared with European whites, and the defect is not accounted for by major coronary heart disease risk factors. Endothelial function may be modulated by novel risk factors in Indian Asians.

Adult↗

PubMed2006

Endothelial function, nitric oxide, and cocoa flavanols.

Endothelial dysfunction is the pathophysiologic principle involved in the initiation and progression of arteriosclerosis, thus endothelial function serves as a "barometer" for cardiovascular health that can be used for the evaluation of new therapeutic strategies. This review provides an introduction to the concept of endothelial dysfunction, and it explores the importance of this prognostic marker in the context of clinical, dietary interventions in humans. Moreover, we summarize and evaluate the findings of various clinical trials that demonstrated an improvement of endothelial dysfunction in subjects with cardiovascular risk factors after the acute and chronic consumption of flavanol-rich foods, including cocoa products, red wine, and tea.

Cacao↗

PubMed2002

Effect of alcohol consumption on endothelial function in men with coronary artery disease.

An inverse relationship between moderate alcohol consumption and coronary artery disease (CAD) has been observed in several epidemiologic studies. Whether improvement of endothelial function is involved in this beneficial effect is unknown. We investigated endothelial function of the brachial artery in 108 men with CAD, 54 of whom consumed alcohol on at least 1 day per week. Brachial artery diameter responses to hyperemic flow (FMD) and to administration of nitroglycerin (NTG) spray were measured using high- resolution ultrasonography. Coronary risk factors and hyperuricemia were present more frequently among drinkers, who also had higher concentrations of triglyceride and apolipoproteins C2, C3, and E. FMD was greater in drinkers (P<0.0001), while NTG-induced dilation was not. Multiple regression analysis showed alcohol consumption to be one of the factors favorably influencing FMD. These findings suggest that alcohol consumption may improve endothelial function in men with CAD.

Aged↗

PubMed2006

Increased brachial-ankle pulse wave velocity is associated with impaired endothelial function in patients with coronary artery disease.

BACKGROUND: Pulse wave velocity and flow-mediated vasodilation (FMD) are widely used as noninvasive modalities for evaluating atherosclerosis. However, it is not known whether pulse wave velocity is related to FMD in patients with coronary artery disease (CAD). Therefore, the present study was designed to investigate the alteration in brachial-ankle pulse wave velocity (baPWV) and endothelial function in CAD patients. METHODS: Thirty-three patients with CAD and thirty control subjects were recruited for this study. baPWV was measured non-invasively using a VP 1000 automated PWV/ABI analyzer (PWV/ABI, Colin Co. Ltd., Komaki, Japan). Endothelial function as reflected by FMD in the brachial artery was assessed with a high-resolution ultrasound device. RESULTS: baPWV was increased in CAD patients compared with control subjects [(1756.1 +/- 253.1) cm/s vs (1495.3 +/- 202.3) cm/s, P < 0.01]. FMD was significantly reduced in CAD patients compared with control subjects [(5.2 +/- 2.1)% vs (11.1 +/- 4.4)%, P < 0.01]. baPWV correlated with FMD (r = -0.68, P < 0.001). The endothelium-independent vasodilation induced by sublingual nitroglycerin in the brachial artery was similar in the CAD group compared with the control group. CONCLUSIONS: CAD is associated with increased baPWV and endothelial dysfunction. Increased baPWV parallels diminished endothelial function. Our data therefore suggest that baPWV can be used as a noninvasive surrogate index in clinical evaluation of endothelial function.

Aged↗

PubMed2001

Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women.

OBJECTIVES: Large scale epidemiological studies suggest that hormone replacement therapy (HRT) reduces cardiovascular events in postmenopausal women. Improvement in endothelial function may contribute to this protective effect. DESIGN: In a prospective, double blind study, 61 healthy postmenopausal women were randomized to receive either oral continuous combined HRT [oestradiol 2 mg and norethisterone acetate (NETA) 1 mg per day] or placebo. Endothelial function, assessed by flow-mediated vasodilation (FMD) of the brachial artery and expression of soluble endothelial cell adhesion molecules (CAM) were determined before, after 3 and 6 months of therapy. RESULTS: The FMD was significantly improved in women on combined HRT (from 5.97% to 10.94% after 3 months and to 10.58% after 6 months; both P < 0.01 versus baseline values) and did not change in the placebo group (6.92% at baseline, 5.86% after 3 and 6.26% after 6 months). After 3 months of combined HRT, significant decreases of 24.6% for E-selectin and 13.9% for intercellular adhesion molecule-1 (ICAM-1) were observed (both P < 0.01 versus baseline values) and were sustained after 6 months of therapy, whilst no differences emerged in the placebo group. CONCLUSIONS: Oestradiol and norethisterone acetate improve endothelial function by both enhancing FMD and reducing the levels of soluble E-selectin and ICAM-1 in healthy postmenopausal women.

Analysis of Variance↗

PubMed2005

Endothelial function and baroreflex sensitivity according to the oral glucose tolerance test in patients with coronary artery disease and normal fasting glucose levels.

Endothelial dysfunction and reduced BRS (baroreflex sensitivity) may be present in patients with CAD (coronary artery disease). The normal fasting glucose level does not exclude abnormal glucose metabolism in patients with CAD. The aim of present study was to evaluate endothelial function and BRS according to glucose metabolism in patients with normal fasting plasma glucose and stable CAD subjected to PTCA (percutaneous transluminal coronary angioplasty). Forty-six consecutive patients who underwent elective PTCA were studied (37 men; mean age 56 years). Endothelial function was assessed non-invasively using the arterial vasodilator response to salbutamol (albuterol). BRS was measured using a cross-correlation method. The extent of coronary narrowing was estimated by calculation of the Gensini score. All patients underwent a 75 g OGTT (oral glucose tolerance test). IGT (impaired glucose tolerance) or diabetes was present in approx. 60% of patients. The vasodilator response to salbutamol, as a measure of endothelial dysfunction, was significantly impaired in patients with IGT or diabetes compared with those with normal glucose tolerance (-0.5+/-1.6% compared with -7.9+/-2.2; P=0.01). Glucose metabolism and age were significant predictors of endothelial dysfunction (R(2)=35.2%, P=0.02). BRS did not differ significantly between patients with normal glucose tolerance and those with IGT or diabetes (6.9+/-1.2 compared with 6.1+/-0.6 ms/mmHg respectively; P=0.669). BRS was negatively correlated with age (r=-0.34, P=0.021) and the Gensini score (r=-0.34, P=0.022). The significant predictors of BRS were Gensini score, age and past myocardial infarction (R(2)=37.02%, P=0.002). Patients with established CAD, normal fasting glucose and IGT or diabetes demonstrated impaired endothelial function which did not correlate with the extent of coronary artery involvement. Conversely, BRS in the study population was not affected by glucose metabolism, but showed an interaction with the extent of coronary narrowing.

Adult↗

PubMed2005

Inhibition of angiotensin-converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure.

ACE (angiotensin-converting enzyme) inhibitors and PDE5 (phosphodiesterase type 5) inhibitors have each been reported to improve endothelial function in cardiovascular disease patients, but the comparative and combined effects of these two classes have not been studied previously. We sought to characterize the acute effects of ramipril alone, sildenafil alone, or their combination on endothelial function in patients with CHF (chronic heart failure). CHF subjects (n=64) were randomized to receive placebo, 10 mg of ramipril alone, 50 mg of sildenafil alone or a combination of ramipril and sildenafil in a double-blind manner. FMD (flow-mediated dilation) of the brachial artery was determined by high-resolution ultrasound imaging before and at 1, 2 and 4 h after administration of the study drug. Ramipril alone increased FMD at 4 h compared with placebo (+2.3+/-1.3%, P=0.02). Sildenafil alone increased FMD at 1, 2 and 4 h compared with placebo (+3.9+/-1.4, +4.6+/-1.8 and +3.7+/-1.3% respectively, all P<0.02). Sildenafil in combination with ramipril increased FMD at 1, 2 and 4 h when compared with placebo (+3.5+/-1.5, +4.5+/-1.8 and +4.8+/-1.3% respectively, all P<0.03). Ramipril and sildenafil both acutely improved FMD in patients with CHF, with additive effects evident at 4 h during combination therapy. Therefore further work to characterize chronic effects of combined ACE and PDE5 inhibition on endothelial function are warranted.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMedDate not supplied

Endothelial function, CRP and oxidative stress in chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased morbidity and mortality in cardiovascular disease (CVD). Apart from traditional risk factors, chronic inflammation, oxidative stress, malnutrition and endothelial dysfunction are important in CVD development in renal patients. Our aim was to investigate the relationship between high sensitivity C-reactive protein (CRP), endothelium dependent vasodilation (EDV) and oxidative stress markers in patients with CKD K/DOQI stage 3-5. METHODS: Measurements of CRP, conjugated dienes (CD), lipid hydroperoxide (LOOH), oxidized low density lipoprotein,glutathione and albumin were performed in 44 consecutive patients with CKD stage 3-5. EDV was measured by methacholine infusion in the brachial artery and venous occlusion plethysmography. RESULTS: Patients with high CRP had significantly lower glomerular filtration rates and albumin, but increased LOOH and CD. In multiple regression analysis, only LOOH and CD remained significant. Patients with poor EDV had increased urea and lower glutathione (GSH). In multiple regression analysis, GSH and urea were independently related to EDV. No correlation was found between CRP and endothelial function. CONCLUSION: CRP was related to lipid peroxidation, while endothelial function was related to intracellular oxidative stress in patients with CKD. CRP and EDV were unrelated to each other. Therefore, CRP and endothelial function could provide complementary prognostic information regarding future cardiovascular disorders in renal patients.

Biomarkers↗

PubMed2003

Determination of endothelial function and early atherosclerotic changes in healthy obese women.

The aim of this study was to determine the associations between vascular endothelial function, intima-media thickness (IMT) of the common carotid artery and anthropometric/metabolic parameters in healthy obese women without obesity-related metabolic complications and age-matched healthy lean controls. Twenty-four obese [body mass index (BMI) > 30 kg/m2; age 31.4 +/- 7.4 yr] and 14 lean (BMI < 24 kg/m2; age 30.5 +/- 7.2 yr) women were studied. All of the subjects had normolipemia. Insulin resistance was calculated according to the homeostasis model assessment (HOMA) formula. Endothelial function was measured by flow-mediated dilation (FMD) of the brachial artery. IMT of the common carotid artery was calculated from high-resolution ultrasound imaging of the two common carotid arteries. Obese and lean women were matched with respect to age, smoking status, blood pressure, glucose, insulin concentrations and HOMA. IMT of common carotid artery was significantly higher (0.56 +/- 0.09 vs 0.45 +/- 0.06 mm, p < 0.001) and FMD (percentage of change from baseline) was significantly lower (13.3 +/- 6.5% vs 25.2 +/- 13.9%,p < 0.001) in the obese subjects. Lipid profile, blood pressure, indirect measurement of insulin resistance, leptin concentrations and anthropometric parameters did not predict the FMD or IMT in the obese and lean groups. It is concluded that even in healthy obese women with a normal metabolic profile, deterioration in endothelial function and early atherosclerotic changes are evident compared with healthy lean counterparts. Some undetermined factors in our study other than obesity-related well-known risk factors could be responsible for this observation.

Adult↗