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Results for “endothelial function”

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PubMed1991

Mechanism of action of angiotensin converting enzyme inhibitors on endothelial function in hypertension.

Hypertension is associated with an endothelial dysfunction characterized by an increased endothelium-dependent contraction and a decreased endothelium-dependent relaxation. Angiotensin converting enzyme (ACE) inhibition with cilazapril or captopril can remarkably improve the endothelial function in spontaneously hypertensive rats (SHRs). The goal of the present study was to investigate whether ACE inhibitors were acting by decreasing endothelium-dependent contraction or by increasing endothelium-dependent relaxation. Endothelial function was estimated by calculating the ratio of maximal contraction to serotonin on isolated aortic rings with endothelium to maximal contraction on paired rings without endothelium, termed the serotonin ratio. The serotonin ratio was greater than 1 in SHRs, indicating the release of a vasoconstrictor substance by the endothelium. This substance was identified as prostaglandin (PG) H2, because the serotonin ratio was significantly decreased by thromboxane (TX) A2/PGH2 receptor antagonists but not by TXA2 synthetase inhibitors. Two weeks of treatment of SHRs with cilazapril led to a marked decrease in the serotonin ratio, although acute administration of cilazaprilat was without any effect. However, after 2 weeks of treatment, the serotonin ratio still could be lowered further by TXA2/PGH2 receptor antagonists, indicating that cilazapril did not act by inhibition of PGH2 synthesis. In contrast, the effect of a 4-week treatment with cilazapril could be completely reversed by inhibiting the action of endothelium-derived relaxing factor with methylene blue. The same result was found after treatment with captopril. We speculate that ACE inhibitors improve endothelial function in SHRs not by inhibiting the synthesis of PGH2 but by increasing the release or the action of endothelium-derived relaxing factor.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Effect of short-term weight loss on the metabolic syndrome and conduit vascular endothelial function in overweight adults.

Impaired vascular endothelial function may be an important mechanism linking obesity to increased cardiovascular risk. We investigated whether short-term weight loss improves conduit artery endothelial dysfunction in overweight adults. Forty-three otherwise healthy overweight patients with a body mass index > or =27 kg/m(2) completed an open-label 3-month trial consisting of a calorie-restricted diet and 120 mg of orlistat taken 3 times daily with meals. Endothelial function and parameters of the metabolic syndrome were measured before and after intervention. Subjects lost 6.6 +/- 3.4% of their body weight. Low-density lipoprotein cholesterol, low-density lipoprotein concentration, fasting insulin, and leptin decreased significantly (all p <0.009), and C-reactive protein decreased (p = 0.22). Conduit vascular function did not change as assessed by flow-mediated dilation (3.86 +/- 3.54 vs 3.74 +/- 3.78%, p = 0.86) and nitroglycerin-mediated dilation (17.18 +/- 5.89 vs 18.87 +/- 7.11%, p = 0.13) of the brachial artery. A moderate degree of weight reduction over 3 months improved the metabolic syndrome profile but not the vascular dysfunction associated with uncomplicated obesity.

Adolescent↗

PubMed2006

Arterial elasticity identified by pulse wave analysis and its relation to endothelial function in patients with coronary artery disease.

Patients with coronary artery disease (CAD) have impaired endothelial function. Arterial elasticity is modulated by endothelial function. The association between arterial elasticity and endothelial function has not been reported in patients with CAD. The present study was designed to investigate whether endothelial dysfunction contributes to impaired arterial elasticity. Thirty patients with CAD and 30 control subjects were recruited. Large and small artery elasticity indices were non-invasively assessed using pulse wave analysis. Brachial artery endothelium-dependent and -independent function were assessed by vascular response to flow-mediated vasodilation (FMD) and sublingual nitroglyceride (NTG), respectively. C1 large artery elasticity index was not different in the CAD group compared with the control group. However, C2 small artery elasticity index was significantly reduced in the CAD group compared with the control group. Flow-mediated vasodilation (FMD) was also impaired in the CAD group compared with the control group. Flow-mediated vasodilation (FMD) in the brachial artery correlated with C2 small arterial elasticity index. But NTG-mediated brachial artery vasodilation was similar between the two groups. The present findings suggest that the patients with CAD have reduced C2 small arterial elasticity index and impaired FMD. Endothelial dysfunction is involved in diminished arterial elasticity, suggesting that C2 small arterial elasticity index is a novel surrogate measure for the clinical evaluation of endothelial function.

Aged↗

PubMed2005

The effect of glucose and mental stress on cutaneous microvascular endothelial function.

Glucose and mental stress, independently, have been found to impair arterial endothelial function (an indicator of vascular health). The present study sought to determine whether the combination of glucose and stress would have a greater effect on microvascular endothelial function than each on its own. To assess endothelial function, surges in skin blood flow (reactive hyperemia), following the release of cuff pressure to the upper arm at 200 mmHg for 5 min, were measured with laser Doppler flowmetry in 40 young, healthy females. Endothelial function did not change significantly following a 5-min mathematics stressor or the consumption of 75 g of glucose. However, the combination of glucose and stress impaired endothelium-dependent dilatation 30 min after glucose consumption. These findings suggest that combinations of vascular risk factors may be more threatening to cardiovascular health than singularly occurring factors.

Adult↗

PubMed2001

Bidirectional cavopulmonary shunt with right ventricular outflow patency: the impact of pulsatility on pulmonary endothelial function.

OBJECTIVE: Although in vitro studies have suggested the importance of flow pulsatility in endothelial function, few reports have focused on pulmonary endothelial function under decreased pulsatile flow after a bidirectional cavopulmonary shunt with or without an additional pulmonary flow source. The purpose of the present study was to assess the pulmonary endothelial function after bidirectional cavopulmonary shunt. METHODS AND RESULTS: Pulmonary vasodilating response was evaluated in 10 patients 0.4 to 7.0 years (median 1.6 years) after bidirectional cavopulmonary shunt who were provided an additional flow source by retaining the pulmonary outflow tract and in 8 control subjects. Average pulmonary flow velocity was measured with a Doppler flow wire placed in the segmental lower lobe pulmonary artery during incremental infusion of acetylcholine (10(-8), 10(-7), 10(-6), and 10(-5) mol/L) and then of nitroglycerin (0.5 and 1.0 microg. kg(-1). min(-1)) after recovery. In the control subjects, a dose-dependent increase in flow velocity was observed in response to acetylcholine (maximum increase was 155% +/- 17% of baseline) and to nitroglycerin (maximum increase was 151% +/- 20% of baseline). In contrast, patients showed a significantly impaired response to acetylcholine (maximum increase was 124% +/- 17% of baseline; P <.01 vs control), whereas the response to nitroglycerin was preserved (138% +/- 12% of baseline; P =.09 vs control). In addition, the maximum response to acetylcholine correlated significantly with the pulmonary pulse pressure (r = 0.89, P <.01) and with the pulmonary flow pulsatility (r = 0.88, P <.01). CONCLUSIONS: These results clearly suggest that patients after bidirectional cavopulmonary shunt show pulmonary endothelial functional attenuation and, of more importance, that decreased pulsatility of cavopulmonary flow is mainly responsible for this endothelial abnormality.

Acetylcholine↗

PubMed2001

Impairment of endothelial function--a possible mechanism for atherosclerosis of a high-fat meal intake.

INTRODUCTION: Endothelial dysfunction is known to occur in patients with coronary artery disease. Flow-mediated dilation of the brachial artery using Doppler ultrasound is a non-invasive technique for the assessment of endothelial function. The objective of the study was to use the above method to evaluate the pathophysiology of high-fat (HF) intake on endothelial function in a local population. A popular local dish "nasi-lemak", a source of high saturated fat content from coconut milk, was chosen to represent a local high-fat meal (LHF). In addition, the effects of a Western high-fat (WHF) ("McDonald's") meal and a low-fat (LF) meal control on endothelial function were studied. MATERIALS AND METHODS: The study population consisted of 10 healthy male non-smoker (mean age 22 +/- 2 years) with normal body mass index, normal fasting sugar and lipid profiles. Nitric oxide dependent flow-mediated dilation and nitric oxide independent (GTN) dilation was assessed by Doppler flow in the brachial artery before and 4 hours after each meal on separate occasions by 2 experienced sonographers blinded to the type of meals. RESULTS: The baseline brachial artery size, baseline vessel flow and increase in flow after cuff deflation were similar for each of the six arterial studies. In response to reactive hyperaemia after cuff deflation, the endothelium-dependent dilation was significantly different between the meals. There was a marked decrease in endothelium-dependent dilation after the WHF meal compared to the LF meal (8.6 +/- 2.2% vs. -0.8 +/- 1.1%, P < 0.006). There was also a marked decrease in endothelium-dependent dilation after the LHF meal compared to the LF meal (7.7 +/- 2.1% vs. -0.8 +/- 1.1%, P < 0.001). When comparing between the two HF meals, the change in endothelium-dependent dilation was not significant (7.7 vs. 8.6%, P = 0.678). GTN-induced dilation was not significantly different before and after the LF, WHF or LHF (0.1 +/- 0.5% vs. 0.2 +/- 0.9% vs. 1.3 +/- 0.5%, P = 0.094). CONCLUSION: The results suggest that in a local population, impairment of endothelial function is a possible mechanism in the pathophysiology of atherosclerosis from HF intake, beyond just affecting lipid levels. This effect is observed after both a LHF and a WHF meal intake. This technique to study endothelial function may be a useful non-invasive screening tool in the study of other HF diet choices and provides further information for the education of the influence of dietary choices on atherosclerosis.

Adult↗

PubMed2005

Endothelial function in highly endurance-trained and sedentary, healthy young women.

Endothelial function is reduced by age, chronic heart failure, coronary artery disease, hypertension or type 2 diabetes, and it is shown that aerobic exercise may reverse this trend. The effect of a high aerobic training status on endothelial function in young, healthy subjects is however less clear. The present study was designed to determine whether endothelial function is improved in highly endurance-trained young women compared to sedentary, healthy controls. Brachial artery diameter was measured in 16 endurance-trained (age: 23.7 +/- 2.5 years, maximal oxygen uptake (VO2max): 60.6 +/- 4.5 ml/kg per min) and 14 sedentary females (age: 23.7 +/- 2.1 years, VO2max: 40.5 +/- 5.6 ml/kg per min) at rest, during flow-mediated dilation (FMD) and after sublingual glycerol trinitrate administration, using high-resolution ultrasound. FMD did not differ between the endurance-trained and the sedentary females (14.8% vs 16.4%, p = NS), despite a substantial difference in VO2max of 50% (p < 0.001). The endurance-trained group possessed however, a 9% larger resting brachial artery diameter when adjusted for body surface area. The results of the present study suggest that endothelial function is well preserved in young, healthy women, and that a high aerobic training status due to long term aerobic training does not improve the dilating capacity any further.

Adult↗

PubMed2006

Divergent effects of angiotensin-converting enzyme inhibition on blood pressure and endothelial function in obese humans.

Endothelial dysfunction is a pivotal early event in the development of atherosclerosis and a characteristic feature of obesity. This study was designed to investigate the effect of angiotensin-converting enzyme (ACE) inhibition on endothelial function in people who were obese but otherwise healthy. We performed a double-blind, randomised, placebo-controlled study examining the effect of the ACE inhibitor perindopril (4 mg per day) on flow-mediated vasodilatation (FMD) of the brachial artery, arterial blood pressure, glucose homeostasis and inflammatory cytokines. Eighteen obese subjects (all body mass index > 30 kg/m2) were randomised to receive perindopril or placebo for four weeks. Perindopril led to a fall in systolic blood pressure from 131 (standard error of mean [SEM] 3) to 117(5) mmHg and diastolic blood pressure from 74(4) mmHg to 68(4) mmHg, both p<0.001. Despite this fall in blood pressure, ACE inhibition had no effect on FMD, 8.2 (1.2)% versus 8.3 (1.5)%, p=0.9. ACE inhibition had no effect on insulin, lipids or circulating cytokines. In healthy obese humans, despite a significant reduction in blood pressure, ACE inhibition had no effect on FMD.

Adult↗

PubMed2003

Effects of transdermal estrogens on endothelial function in postmenopausal women with coronary disease.

OBJECTIVE: Oral estrogens improve endothelial function, and for this reason may be considered cardioprotective; however, in women with coronary heart disease there may also be an increase in the risk of thrombosis. Although transdermal estrogen administration may decrease this adverse effect, there are few data on endothelial function in women with coronary heart disease treated using such therapy. This study aimed to report the endothelial response in postmenopausal women with coronary heart disease treated with transdermal estrogen. MATERIALS AND METHODS: This was a double-blind, prospective, randomized study. Eighteen patients with a history of acute coronary syndrome and nine healthy women were studied over 4 weeks. Coronary patients were assigned at random to receive a patch containing either 50 microg estradiol or placebo on a weekly basis. Endothelial function was assessed by flow-mediated vasodilatation of the brachial artery. Baseline blood flow (brachial artery diameter) was measured after 30 min rest and following ischemia, prior to treatment and after 4 weeks. RESULTS: Flow-mediated vasodilatation in normal patients was 17.8%, whereas in women with coronary disease it was 1.2% (p = 0.0001). Arterial diameter for the resting period in coronary disease subjects increased from 4.22 +/- 0.59 to 4.41 +/- 0.56 mm (p < 0.004) after 4 weeks of estrogen therapy, whereas, in women receiving placebo, it did not change. Flow-mediated vasodilatation in the estrogen group was 3.4% and in the placebo group was 0.5% (p = 0.05). CONCLUSIONS: Transdermal estrogen may improve endothelial function in women with coronary heart disease.

Administration, Cutaneous↗

PubMed2005

Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes.

BACKGROUND: Endothelial dysfunction and arterial stiffening are commonly observed in type 2 diabetes. These abnormalities might be secondary to increased plasma concentrations of homocysteine. We sought to determine whether oral folic acid supplementation, by lowering homocysteine levels, enhanced endothelial function and reduced arterial stiffness in type 2 diabetes. METHODS: Twenty-six type 2 diabetic patients (age 56.5 +/- 0.9 years, diabetes duration 5.5 +/- 0.6 years, means +/- SEM) with no history of cardiovascular disease received 5 mg/d of oral folic acid or placebo for 4 weeks in a double-blind, randomized controlled, parallel group trial. The following parameters were measured before and after treatment: 1) endothelial function (forearm arterial blood flow during local intra-arterial administration of endothelium-dependent [acetylcholine 1.5, 4.5, and 15 microg/min] and endothelium-independent [sodium nitroprusside 1, 2, and 4 microg/min] vasodilators); and 2) carotid-radial and carotid-femoral pulse wave velocity. RESULTS: Folic acid reduced plasma homocysteine concentrations and enhanced endothelium-dependent vasodilatation during each acetylcholine infusion rate (mean and 95% confidence interval post versus pretreatment differences in forearm arterial blood flow ratio between the infused and control arm +0.19 (0.03-0.35), P < .01; +0.39 (0.02-0.81), P < .05; and +0.40 (0.09-0.89), P < .05, respectively). Endothelium-independent vasodilatation and pulse wave velocity were not affected. No significant changes in forearm arterial blood flow and pulse wave velocity were observed in the placebo group. Multiple regression analysis showed that changes in folic acid, but not homocysteine, concentrations independently described changes in maximal endothelium-dependent vasodilatation. CONCLUSIONS: Short-term oral folic acid supplementation significantly enhances endothelial function in type 2 diabetic patients, independent of homocysteine lowering.

Acetylcholine↗

PubMed2006

Steroid therapy improves endothelial function in patients with biopsy-proven giant cell arteritis.

OBJECTIVE: Endothelial dysfunction has been found to be present in subjects with both small and medium-size blood vessel vasculitides. We assess whether endothelial dysfunction was also present in patients with biopsy-proven giant cell arteritis (GCA) and whether it might be improved following steroid treatment. METHODS: Endothelial function was determined in cross-sectional and longitudinal studies of 6 patients with biopsy-proven GCA diagnosed between January and May 2002 by measuring flow-mediated endothelial-dependent and independent vasodilatation (EDV and EIV) by brachial ultrasonography. Patients were assessed for endothelial function within 48 hours after the onset of steroid therapy, 4 weeks after the onset of steroid therapy, and 2 years after the disease diagnosis. RESULTS: EDV was significantly impaired in patients with GCA compared with 12 matched controls [mean 2.9%, median 2.45% (range 2.1% to 4.7%) vs mean 6.5%, median 6.6% (range 3.9% to 9.3%) in matched controls; p = 0.002]. However, no significant difference existed between patients and controls in EIV. Significant improvement of EDV after the suppression of inflammation was achieved. At Week 4 after the onset of steroid therapy all 6 patients showed enhanced responses (p = 0.028). This improvement of EDV was still present when steroid treatment was ended, 2 years after diagnosis. CONCLUSION: Endothelial function is significantly impaired in individuals with active biopsy-proven GCA. The results highlight the importance of steroid therapy to improve endothelial function after suppression of the inflammation of GCA.

Aged↗

PubMed2006

Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women.

Endothelial dysfunction characterizes many disease states including subclinical atherosclerosis. The consumption of flavanol-rich cocoa and cocoa-based products has been shown to improve endothelial function in both compromised and otherwise normal, healthy individuals when administered either acutely or over a period of several days, or weeks. Women experience increased risk for cardiovascular disease after menopause, which can be associated with endothelial dysfunction. Whether a flavanol-rich cocoa-based product can improve endothelial function in hypercholesterolemic postmenopausal women is not known. The purpose of the present study was to determine whether chronic dietary administration of flavanol-rich cocoa improves endothelial function and markers of cardiovascular health in hypercholesterolemic postmenopausal women. Thirty-two postmenopausal hypercholesterolemic women were randomly assigned to consume a high-flavanol cocoa beverage (high cocoa flavanols (CF)--446 mg of total flavanols), or a low-flavanol cocoa beverage (low CF--43 mg of total flavanols) for 6 weeks in a double-blind study (n=16 per group). Endothelial function was determined by brachial artery-reactive hyperemia. Plasma was analyzed for lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), hormones (follicle-stimulating hormone), total nitrate/nitrite, activation of cellular adhesion markers (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, E-Selectin, P-Selectin), and platelet function and reactivity. Changes in these plasma markers were then correlated to brachial reactivity. Brachial artery hyperemic blood flow increased significantly by 76% (P<0.05 vs. baseline) after the 6-week cocoa intervention in the high CF group, compared with 32% in the low CF cocoa group (P=ns vs. baseline). The 2.4-fold increase in hyperemic blood flow with high CF cocoa closely correlated (r2=0.8) with a significant decrease (11%) in plasma levels of soluble vascular cell adhesion molecule-1. Similar responses were not observed after chronic use of low CF. There were no significant differences between high and low CF in other biochemical markers and parameters measured. This study is the first to identify beneficial vascular effects of flavanol-rich cocoa consumption in hypercholesterolemic postmenopausal women. In addition, our results suggest that reductions in plasma soluble vascular cell adhesion molecule-1 after chronic consumption of a flavanol-rich cocoa may be mechanistically linked to improved vascular reactivity.

Beverages↗

PubMed2005

Evaluation of arterial endothelial function using transit times of artificially induced pulses.

Impairment of arterial endothelial function is an early event in atherosclerosis and correlates with the major risk factors for cardiovascular disease. The most widely employed non-invasive measure of endothelial function involves brachial artery (BA) diameter measurement using ultrasound imaging before and after several minutes of blood flow occlusion. The change in arterial diameter is a measure of flow-mediated vasorelaxation (FMVR). The high between-laboratory variability of results and cost of instrumentation render this technique unsuitable for routine clinical use. We induce artificial pulses at the superficial radial artery using a linear actuator. An ultrasonic Doppler stethoscope detects these pulses 10-30 cm proximal to the point of pulse induction. The delay between pulse application and detection provides the pulse transit time (PTT). By measuring PTT before and after 5 min of BA occlusion and ensuing reactive hyperemia, FMVR may be measured based on the changes in PTT caused by changes in vessel caliber, smooth muscle tone and wall thickness. We (1) validate the sensitivity of this technique to arterial wall tone using sublingual nitroglycerin and (2) compare measurements of endothelial function to ultrasound BA diameter measurements in 12 human subjects. The PTT-based method is verified to measure arterial wall tone and is shown to provide 37% greater sensitivity (p < 0.05) to FMVR than BA diameter measurements. By measuring the change in pulse transit time before and after endothelial stimulus, a sensitive, reproducible and convenient measure of endothelial function may be obtained at a low cost.

Blood Flow Velocity↗

PubMed2007

Effect of physical activity and muscle morphology on endothelial function and arterial stiffness.

Physically active persons have a reduced risk of atherosclerotic disease. Arterial stiffness and endothelial dysfunction are important risk factors for cardiovascular disease. A high proportion of type I (slow-twitch) muscle fibers in skeletal muscle is associated with a favorable cardiovascular risk profile. We tested physical activity and muscle fiber-type distribution as determinants of endothelial function and arterial stiffness in middle-aged men. Fifty-four men (median age 58) who underwent a muscle biopsy in 1984 were re-studied in 2003. Aortic pulse wave velocity (PWV) and pulse wave reflection were assessed by applanation tonometry. Endothelial function was tested by examining the effects of salbutamol and nitroglycerin on pulse wave reflection. In multiple regression analyses aortic PWV (R2=0.51) correlated positively with age (P=0.017), BMI (P=0.001), and systolic blood pressure (P=0.004). A high augmentation index (R2=0.33) was associated with smoking (P<0.001), high LDL cholesterol (P=0.02), and elevated diastolic blood pressure (P=0.03). Impaired endothelial function (R2=0.37) was associated with high age (P=0.04), high LDL cholesterol (P=0.017), high triglycerides (P=0.027), and high physical activity (P=0.005). Muscle fiber-type distribution is not a determinant of arterial stiffness or endothelial function. Impaired endothelial function was observed in physically active men, underlining the need for further research.

Aged↗

PubMed2001

A noninvasive measurement of reactive hyperemia that can be used to assess resistance artery endothelial function in humans.

We demonstrated that endothelial function in patients with essential hypertension is impaired by a decrease in nitric oxide production using both reactive hyperemia and acetylcholine infusion methods. This noninvasive method of evaluating reactive hyperemia is a useful alternative to intra-arterial infusions of vasoactive agents in the assessment of resistance vessels' endothelial function in forearm circulation.

Acetylcholine↗

PubMed2001

Usefulness of visceral obesity (waist/hip ratio) in predicting vascular endothelial function in healthy overweight adults.

Vascular endothelial dysfunction (VED) is associated with obesity; however, its etiology remains controversial. By determining the predictors of fasting and postprandial endothelial function in overweight adults without other cardiovascular risk factors, we were able to investigate novel mechanisms directly linking obesity to VED. Thirty-two healthy adults (body mass index [BMI] > or =27 kg/m(2)) underwent determination of fasting low-density lipoprotein (LDL) particle size, high sensitivity C-reactive protein levels, anthropometric measurements, and endothelial function by flow-mediated dilation (FMD) of the brachial artery. Postprandial lipemia and FMD were measured 4 hours after ingestion of a high-fat meal. Blood pressures and fasting levels of lipoproteins, glucose, insulin, and fatty acids were within normal limits in all subjects. An abdominal fat pattern, as determined by an increased waist/hip ratio (WHR), was the sole significant predictor of FMD (r = -0.58, p = 0.001), despite no significant correlation between whole body obesity (BMI) and FMD. At comparable levels of BMI, obese subjects with a WHR > or =0.85 had a significantly blunted FMD compared with those with a WHR <0.85 (3.93 +/- 2.85% vs 8.34 +/- 5.47%, p = 0.016). Traditional coronary risk factors, C-reactive protein, postprandial lipemia, and LDL particle size did not predict FMD. We found no appreciable alteration in the postprandial state from fasting FMD (6.31 +/- 4.62% vs 6.25 +/- 5.47%, p = 0.95). The same results were found when women were analyzed alone. Increased abdominal adiposity determined by a simple WHR is a strong independent predictor of VED even in healthy overweight adults; this is a finding unexplained by alterations in conventional risk factors, systemic inflammation, or the atherogenic lipoprotein pattern.

Adult↗

PubMed2006

Endothelial function and biochemical vascular markers in first-degree relatives of type 2 diabetic patients: the effect of exercise training.

Endothelial dysfunction (ED) is associated with the presence of atherosclerosis. However, ED is also considered a sign of the early vascular changes preceding atherosclerosis. By measuring flow-mediated vasodilation (FMD) and circulating markers of endothelial function we sought to explore whether impaired endothelial function is already present in healthy subjects at increased risk of developing type 2 diabetes mellitus. Furthermore, we aimed to assess the impact of short-term lifestyle intervention (10 weeks endurance exercise) on the potentially primary defects of endothelial function. Twenty-nine healthy but insulin-resistant first-degree relatives of patients diagnosed with type 2 diabetes mellitus (33 +/- 5 years; body mass index, 26.3 +/- 1.6 kg/m2) were compared with 19 control subjects without a family history of diabetes mellitus (31 +/- 5 years; body mass index, 25.8 +/- 3.0 kg/m2). At baseline the von Willebrand factor was significantly increased in the relatives (P < .05). Furthermore, mannose-binding lectin (P = .06), soluble intercellular adhesion molecule 1 (P = .08), and osteoprotegerin (P = .08) tended to be increased in relatives. The following markers of endothelial function were comparable at baseline: FMD, C-reactive protein, plasminogen activator inhibitor 1, and soluble vascular cell adhesion molecule 1. Exercise training resulted in a decrease in mannose-binding lectin (P = .02) and osteoprotegerin (P < .01) in relatives only, whereas other biochemical markers were unaffected in both groups. Moreover, the relatively high-intensity exercise training tended weakly to reduce FMD in the relatives (P = .15). In conclusion, healthy subjects predisposed for type 2 diabetes mellitus show only minor signs of endothelial dysfunction. Under these almost normal vascular conditions, exercise training has little effect on endothelial function.

Adult↗

PubMed2006

High- but not low-dose folic acid improves endothelial function in coronary artery disease.

BACKGROUND: While folic acid (FA) reduces plasma homocysteine (Hcy), whether the simultaneous improvement in endothelial function is dependent on Hcy lowering per se is questionable. In the present study the relationship between FA dose, Hcy lowering and endothelial function in patients with coronary artery disease (CAD) was investigated. MATERIALS AND METHODS: Eighty-four patients with CAD received either 400 microg FA or 5 mg placebo daily for a 6-week treatment period. A further 44 patients with CAD received either 100 mg kg(-1) day(-1) of betaine or placebo for a 6-week treatment period. Flow-mediated dilatation (FMD), a measure of endothelial function, was assessed before and after the 6-week periods. Isometric tension and Western blotting were used to investigate the effect of FA on endothelial function and endothelial nitric oxide synthase (eNOS) dimerization in isolated rabbit aortic rings and cultured porcine aortic endothelial cells (PAEC), respectively. RESULTS: Both 400 micro g day(-1) and 5 mg day(-1) FA significantly increased plasma folate and decreased plasma Hcy. The FMD improved significantly after 6 weeks' treatment of 5 mg day(-1) FA but did not correlate with the reduction in Hcy. There was no change in FMD in either the 400 micro g FA or placebo group. In a subgroup analysis of 11 patients in the betaine group, despite a reduced Hcy, a significant impairment in FMD was observed. In the in vitro studies FA, but not betaine, reversed methionine-induced endothelial dysfunction. Moreover, the FA promoted eNOS dimerization in cultured PAEC. CONCLUSIONS: These data suggest that FA dose-dependently improves endothelial function in CAD via a mechanism independently of Hcy lowering. It may involve promotion of eNOS dimerization.

Aged↗