Index Of Endothelial Function Research Articles

Relationship between upper and lower limb conduit artery vasodilator function in humans

Brachial artery flow-mediated dilation (FMD) is a strong predictor of future cardiovascular disease and is believed to represent a "barometer" of systemic endothelial health. Although a recent study [Padilla et al. Exp Biol Med (Maywood) 235: 1287-1291, 2010] in pigs confirmed a strong correlation between brachial and femoral artery endothelial function, it is unclear to what extent brachial artery FMD represents a systemic index of endothelial function in humans. We conducted a retrospective analysis of data from our laboratory to evaluate relationships between the upper (i.e., brachial artery) vs. lower limb (superficial femoral n = 75; popliteal artery n = 32) endothelium-dependent FMD and endothelium-independent glyceryl trinitrate (GTN)-mediated dilation in young, healthy individuals. We also examined the relationship between FMD assessed in both brachial arteries (n = 42). There was no correlation between brachial and superficial femoral artery FMD (r(2) = 0.008; P = 0.46) or between brachial and popliteal artery FMD (r(2) = 0.003; P = 0.78). However, a correlation was observed in FMD between both brachial arteries (r(2) = 0.34; P < 0.001). Brachial and superficial femoral artery GTN were modestly correlated (r(2) = 0.13; P = 0.007), but brachial and popliteal artery GTN responses were not (r(2) = 0.08; P = 0.11). Collectively, these data indicate that conduit artery vasodilator function in the upper limbs (of healthy humans) is not predictive of that in the lower limbs, whereas measurement of FMD in one arm appears to be predictive of FMD in the other. These data do not support the hypothesis that brachial artery FMD in healthy humans represents a systemic index of endothelial function.

The exercise dose affects oxidative stress and brachial artery flow-mediated dilation in trained men

The aim of this investigation was to establish whether changes in oxidative stress and endothelial function following acute aerobic exercise are dose-dependent. Ten healthy trained men completed four exercise sessions: 50% VO(2peak) for 30 min (moderate intensity moderate duration, MIMD), 50% VO(2peak) for 60 min (moderate intensity long duration, MILD), 80% VO(2peak) for 30 min (high intensity moderate duration, HIMD), and 80% VO(2peak) for the time to reach the caloric equivalent of MIMD (high intensity short duration, HISD). Thiobarbituric acid reactive substances (TBARS) were measured as an index of oxidative stress and brachial artery flow-mediated dilation (FMD) was assessed as an index of endothelial function. Variables were measured at baseline, immediately post-exercise, 1 and 2 h post-exercise. Both HIMD (14.2 ± 2.5 μmol/L) and HISD (14.7 ± 1.9 μmol/L) TBARS differed from MIMD (11.8 ± 1.5 μmol/L) immediately post-exercise. TBARS increased from pre to immediately post-exercise for HIMD (12.6 ± 2.1 vs.14.2 ± 2.5 μmol/L) and HISD (12.3 ± 2.8 vs. 14.7 ± 1.9 μmol/L). Both MIMD (7.2 ± 2.2%) and HISD (7.6 ± 2.7%) FMD immediately post-exercise were greater than HIMD (4.7 ± 2.2%). An increase of FMD from pre to immediately post-exercise was found for MIMD (5.0 ± 2.5 vs. 7.2 ± 2.2%) and HISD (5.9 ± 2.4 vs. 7.6 ± 2.7%). These data suggest that acute exercise-induced TBARS are exercise intensity-dependent whereas FMD appears to improve following energy expenditure equivalent to 30 min 50% VO(2peak), regardless of intensity or duration.

Resistance and aerobic exercise protects against acute endothelial impairment induced by a single exposure to hypertension during exertion

Resistance and aerobic exercise is recommended for cardiovascular health and disease prevention. However, the accompanying increase in arterial pressure during resistance exercise may be detrimental to vascular health. This study tests the vascular benefits of aerobic compared with resistance exercise on preventing impaired vascular function induced by a single weight lifting session that is associated with acute hypertension. Healthy, lean sedentary (SED) subjects, weight lifters, runners (>15 miles/wk), and cross trainers (chronic aerobic and resistance exercisers), underwent a single progressive leg press weight lifting session with blood pressure measurements. Brachial artery flow-mediated vasodilation (FMD; an index of arterial endothelial function) was determined using ultrasonography immediately before and after weight lifting. Sublingual nitroglycerin (0.4 mg) was used to determine endothelium-independent dilation after weight lifting. All subjects were normotensive with similar blood pressure responses during exercise. Baseline FMD was lower in runners (5.4 ± 0.5%; n = 13) and cross trainers (4.44 ± 0.3%; n = 13) vs. SED (8.5 ± 0.8%; n = 13; P = 0.037). Brachial FMD improved in conditioned weight lifters (to 8.8 ± 0.9%; P = 0.007) and runners (to 7.6 ± 0.6%; P < 0.001) but not cross trainers (to 5.3 ± 0.6%; P = NS) after acute hypertension. FMD was decreased in SED (to 5.7 ± 0.4%; P = 0.019). Dilation to nitroglycerin was similar among groups. These data suggest that endothelial responses are maintained after exposure to a single bout of weight lifting in resistance and aerobic athletes. Resistance and aerobic exercise may confer similar protection against acute vascular insults such as exertional hypertension.

Irbesartan improves endothelial dysfunction, abnormal lipid profile, proteinuria and liver dysfunction in Zucker diabetic fatty rats independent of glucose and insulin levels

Treatment with angiotensin type 1 receptor blockers (ARBs) is known to improve renal dysfunction and glucose metabolism in obese diabetic animal models and humans. This study examined the effects of irbesartan, a unique ARB with PPARγ activation, on endothelial dysfunction, renal dysfunction, abnormal lipid profile, and liver dysfunction in obese fa/fa Zucker diabetic fatty (ZDF) rats. ZDF rats were administered irbesartan (30 mg/kg/day p.o.) for 12 weeks. Blood pressure, glucose metabolism, lipid profile and renal function were measured every 4 weeks. Response of mesenteric artery rings to acetylcholine was also evaluated as an index of endothelial function after 12 weeks of treatment. Although irbesartan did not affect glucose and insulin levels in both glucose and insulin tolerance tests, decreases in systolic blood pressure, dyslipidemia, and urinary protein excretion were noted from 4 weeks after the start of treatment and continued until 12 weeks. Endothelial and liver dysfunctions were also improved after 12 weeks of treatment. Compared to previous reports showing the effects of irbesartan at later time points such as 6 or 12 months, the present study demonstrated that a low-dose of irbesartan had favorable effects from the early period of treatment, independent of glucose metabolism. Our findings suggest that a low-dose of irbesartan improves diabetic complications quickly after starting treatment, and may support the use of irbesartan for preventing progression of diabetic complications.

Association between asymmetric dimethylarginine and indices of vascular function in patients with essential hypertension

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and is associated with endothelial dysfunction. The aim of the present study was to investigate the relationship between ADMA, indices of arterial stiffness, endothelial function and carotid artery intima-media thickness (IMT) in hypertension patients. Eighty middle-aged (47 ± 10 years) untreated patients with mild to moderate essential hypertension underwent routine physical examination, pulse wave analysis (PWA), measurement of aortic pulse wave velocity (PWV) and IMT. In PWA, administration of salbutamol and nitroglycerine was used to assess endothelium-dependent (EDV) and endothelium-independent vasodilation, respectively. In univariate analysis, ADMA was correlated with EDV (r = −0.26; p = 0.02) and IMT (r = 0.32; p = 0.007). In multiple regression analysis, ADMA was independently associated with the female gender, EDV, IMT and total cholesterol (R2 = 0.30; p < 0.001). No correlation was detected between ADMA and augmentation index, central/brachial blood pressure or aortic PWV. In hypertension patients, ADMA is independently correlated with IMT and EDV. Thus, ADMA is a marker of endothelial dysfunction and intima-media thickening in patients with hypertension.

Long-term smoking causes more advanced coronary endothelial dysfunction in middle-aged smokers compared to young smokers

Smoking cessation has been shown to normalize the coronary endothelial dysfunction in healthy young smokers. However, its effect has not been explored in middle-aged smokers with a longer history of smoking. Therefore, we compared the effects of smoking cessation on coronary vasomotor response between both young and middle-aged smokers and identified the predictor for its improvement. This study investigated 14 young healthy smokers (age 25.2 ± 2.3 years), 13 middle-aged smokers (age 42.0 ± 6.5 years) and 10 non-smokers. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography (PET). At baseline, the ratio of MBF during the cold pressor test (CPT) to that at rest (MBF(CPT/rest)), the index of coronary endothelial function, was significantly decreased in both young and middle-aged smokers compared to non-smokers (1.24 ± 0.20 and 1.10 ± 0.39 vs 1.53 ± 0.18, p < 0.05 and p < 0.001, respectively). The ratio of MBF during adenosine triphosphate infusion to that at rest was significantly decreased in middle-aged smokers compared to young smokers and non-smokers (3.34 ± 1.52 vs 4.43 ± 0.92 and 4.69 ± 1.25, p < 0.05, respectively). MBF(CPT/rest) at 1 month after smoking cessation significantly increased in young smokers, but not in middle-aged smokers. By multivariate analysis, baseline serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) was an independent predictor for the changes in MBF(CPT/rest) after smoking cessation (β = -0.45, p < 0.05). Coronary endothelial dysfunction was reversible by short-term smoking cessation in young smokers, but not in middle-aged smokers, which was associated with serum MDA-LDL levels. Long-term smoking exposure could lead to more advanced coronary endothelial dysfunction and atherosclerosis possibly via oxidative stress.

Postprandial Endothelial Function: The Effect of Various Types of Fat and of Red Wine Intake on Flow- Mediated Dilation in Healthy Volunteers

Background : Current evidence suggests that postprandial lipid composition may have either atherogenic or anti-atherogenic properties. This study investigated the acute postprandial effect of three different types of fat (saturated, mono-unsaturated, poly-unsaturated) and of red wine upon endothelial function of healthy subjects. Methods: We fed 21 healthy young subjects four meals containing 1000 kcal and 50 g fat each. Three of the meals contained different fat sources: yellow cheese (saturated fat-meal A), olive oil (monounsaturated fat-meal B) and margarine (polyunsaturated fat-meal C). The fourth meal contained the same amount of saturated fat as the first one together with 250 cc of red wine (meal D). We measured serum lipoproteins, with the use of standard laboratory techniques. Β rachial artery flow-mediated vasodilation (FMD), an index of endothelial function, was also assessed with B-Mode vascular ultrasound. All measurements were performed before, 2 and 4 h after each meal Results: All four meals significantly raised plasma triglycerides. Meal A was associated with a decrease in FMD 2 and 4 hours after its intake ( 16.5 ± 5% vs. 13 ± 4% vs. 12.3 ± 6% , p= 0.030) while with meal D FMD profoundly decreased 2 hours postprandially with a rapid return to baseline levels at 4 hours (14.3 ± 9.5 vs. 8.6 ± 5.5 vs. 12.6 ± 7.5 , p=0.214) . This type of response was associated with a concomitant increase of basal brachial artery diameter at 2 hours postpandially ( 3.7±0.6 mm vs 4.2±0.7 mm vs 3.9±0.7mm at 0, 2 and 4 hours respectively , p=0.000 ). Meals B and C did not significantly affect FMD. Conclusions. Saturated fat acutely decreases FMD while mono-unsaturated and poly-unsaturated fat do not have any harmful effect on endothelium. The concomitant intake of red wine with saturated fat is associated with a delayed counteracting effect on lipid-induced postprandial endothelial dysfunction.

Should we be on the fence or can we open the gate? Evidence that QRS gating in FMD analysis is not essential

the function of arterial endothelial cells is now recognized as an important factor in the pathogenesis of atherosclerosis. Almost two decades ago, Celermajer and colleagues ([2][1]) introduced a noninvasive assessment technique to evaluate endothelial function in humans. In this test, the magnitude

N-3 polyunsaturated fatty acids early supplementation improves ultrasound indices of endothelial function, but not through NO inhibitors in patients with acute myocardial infarction: N-3 PUFA supplementation in acute myocardial infarction.

Our aim was to evaluate early initiated one month n-3 polyunsaturated fatty acids (PUFA) supplementation effects on ultrasound indices of endothelial function and serum asymmetric dimethylarginine (ADMA) levels in patients with acute myocardial infarction (AMI). Forty patients with AMI and successful percutaneous coronary intervention (PCI) were recruited into the study and randomized to the study group (group P; n = 20; standard therapy + n-3 PUFA 1 g daily) or the control group (group C; n = 20; standard therapy). Ultrasound indices of endothelial function: flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NMD) and serum ADMA concentrations (ELISA) were obtained before and after one month (30 ± 1 days) therapy (presented as means ± standard deviations). There was a significant difference between both groups in mean delta (baseline/after one month) FMD (P: 8.1 ± 12.6% vs C: -2.2 ± 11.8%; p = 0.02) with no difference in mean delta NMD (P: 3.3 ± 11.9% vs 0.66 ± 14.3%; p = 0.53). We found also a significant increase in mean FMD (7.4 ± 6.4 to 15.5 ± 10.5%; p = 0.02) with a nonsignificant change in mean NMD values (26.9 ± 12.1 to 30.2 ± 14.0%; p = 0.24) after 1-month therapy with n-3 PUFA. FMD and NMD mean values did not change in control patients (FMD: 11.6 ± 6.1% to 9.4 ± 8.0%; p = 0.5 NMD: 25.1 ± 11.4% to 25.8 ± 14.0%; p = 0.84). The comparison of mean delta ADMA values for both groups revealed no differences (P: 6.2 ± 9.7 μmol/l vs C: 3.6 ± 9.5 μmol/l; p = 0.43). Mean serum ADMA concentrations were significantly increased after 1-month therapy in the group P (P: 2.1 ± 1.8 to 8.3 ± 9.7 μmol/l; p = 0.001; C: 4.5 ± 7.1 to 8.1 ± 9.5 μmol/l; p = 0.09). However, there was a nonsignificant difference in mean baseline serum ADMA levels between both groups (P: 2.1 ± 1.8 μmol/l vs C: 4.5 ± 7.1 μmol/l; p = 0.32). There were no significant correlations between FMD, NMD, ADMA levels and demographic, clinical or biochemical parameters. Early and short-term n-3 PUFA supplementation improved ultrasound indices of endothelial function without affecting serum ADMA levels in patients with AMI and successful primary PCI.

The relation of intima-media thickness with endothelial function and left ventricular mass index

We aimed to investigate the relation of brachial artery intima-media thickness (IMT) with endothelial function and left ventricular mass (LVM). Fifty-four stage I-II hypertensive patients according to JNC VII who were not taking any medication and 27 age and sex-matched healthy controls were included to this cross-sectional observational study. IMT was measured by the same radiologist who was unaware of the patient's clinical status by using high resolution ultrasound machine. Endothelial function was evaluated by flow mediated dilation (endothelium-dependent vasodilatation, FMD). LVM was calculated by using Devereux method. LVM index (LVMI) was obtained by dividing LVM to body surface area. Mann-Whitney U test was used to compare continuous variables, qualitative variables were compared by Chi-square test and the relations of parameters were evaluated by multiple linear regression analysis. Both groups (hypertensive and control) were similar with respect to age, sex, left ventricular ejection fraction. IMT was significantly higher in hypertensive group (0.43+/-0.09 vs 0.33+/-0.06 mm; p<0.001). FMD values were also significantly different between hypertensive and control groups (4+/-4% vs 13+/-12%; p<0.001). LVMI was significantly different between hypertensive and control groups LVMI (124 +/- 5 vs 99+/-6 gr/m2, p=0.002). The correlation between IMT and FMD (r=0.260; p=0.026) and IMT and LVMI (r =0.348; p=0.004) were statistically significant. A correlation was found between IMT and LVMI independently of other variables (beta=105; p=0.004) when LVMI was accepted as dependent variable in multivariate linear regression analysis (R2=0.570, p<0.001). According to this finding, the 105 units increase in LVMI occurs when IMT increases by 1 mm. Brachial artery IMT is related to endothelial function and LVM. According to these data, any negative changes of the IMT may reflect the similar negative changes in other parameters.

Long-term intervention with Lactobacillus helveticus fermented milk reduces augmentation index in hypertensive subjects.

Background:The milk casein-derived biologically active tripeptides, isoleucyl-prolyl-proline (Ile-Pro-Pro) and valyl-prolyl-proline (Val-Pro-Pro), have documented antihypertensive effect probably related to reduced angiotensin formation. It has been suggested that these tripeptides may reduce arterial stiffness and improve endothelial function. Our aim was to evaluate whether the milk-based drink containing Ile-Pro-Pro and Val-Pro-Pro influence arterial stiffness, measured as augmentation index (AIx), and endothelial function in man.Methods:In a double-blind parallel group intervention study, 89 hypertensive subjects received daily peptide milk containing a low dose of tripeptides (5 mg/day) for 12 weeks and a high dose (50 mg/day) for the following 12 weeks, or a placebo milk drink to titrate the dose–response effect. Arterial stiffness was assessed by pulse wave analysis at the beginning and end of each intervention period. Endothelial function was tested by examining pulse wave reflection response to sublingual nitroglycerin and salbutamol inhalation. Blood pressure was measured by using office and 24-h ambulatory blood pressure measurement.Results:At the end of the second intervention period, AIx decreased significantly in the peptide group compared with the placebo group (peptide group −1.53% (95% confidence interval (CI) −2.95 to −0.12), placebo group 1.20% (95% CI 0.09–2.32), P=0·013). No change in endothelial function index was observed (peptide group 0.02 (95% CI −0.06 to 0.08), placebo group 0.04 (95% CI −0.04 to 0.12), P=0.85). There were no statistically significant differences between the effects of the peptide and placebo treatment on office and 24-h ambulatory blood pressure.Conclusions:Long-term treatment with Lactobacillus helveticus-fermented milk containing bioactive peptides reduces arterial stiffness expressed as AIx in hypertensive subjects.

Acute and long-term effects of grape and pomegranate juice consumption on vascular reactivity in paediatric metabolic syndrome

This study, which to the best of our knowledge is the first of its kind, aimed to determine the acute and long-term effects of the consumption of grape and pomegranate juices on endothelium function in adolescents with metabolic syndrome, and to compare the effects of these two kinds of juices. This randomised controlled clinical trial was conducted in 2008 among 30 adolescents, aged 12-15 years, with metabolic syndrome. Participants were randomly assigned to two groups of equal number; one group was asked to drink 18 millilitre per kilogram per day of natural grape juice and the other group was asked to drink 240 millilitre per day of natural pomegranate juice once daily for 1 month. Juices were homemade without any added sweetener. Basal brachial artery dimension and flow-mediated dilation as an index of endothelial function and endothelial-dependent dilation after receiving nitoglycerin spray were evaluated by high-resolution B mode ultrasonography before juice consumption, 4 hours and 30 days after regular daily consumption. Flow-mediated dilation at 90 seconds and after nitoglycerin significantly improved at 4 hours and at 1 month after drinking both kinds of juices, without significant difference between the two groups. The change at 1 month versus 4 hours was significant only in the grape juice group. Daily consumption of diets rich in antioxidants might improve endothelial function in adolescents with metabolic syndrome. These effects began as soon as 4 hours after juice consumption. Such beneficial effects should be considered in dietary recommendations for the paediatric age group, notably in obese individuals.

Shear Stress Mediates Endothelial Adaptations to Exercise Training in Humans

Although episodic changes in shear stress have been proposed as the mechanism responsible for the effects of exercise training on the vasculature, this hypothesis has not been directly addressed in humans. We examined brachial artery flow-mediated dilation, an index of NO-mediated endothelial function, in healthy men in response to an acute bout of handgrip exercise and across an 8-week period of bilateral handgrip training. Shear stress responses were attenuated in one arm by cuff inflation to 60 mm Hg. Similar increases were observed in grip strength and forearm volume and girth in both limbs. Acute bouts of handgrip exercise increased shear rate (P<0.005) and flow-mediated dilation percentage (P<0.05) in the uncuffed limb, whereas no changes were evident in the cuffed arm. Handgrip training increased flow-mediated dilation percentage in the noncuffed limb at weeks 2, 4, and 6 (P<0.001), whereas no changes were observed in the cuffed arm. Brachial artery peak reactive hyperemia, an index of resistance artery remodeling, progressively increased with training in the noncuffed limb (P<0.001 and 0.004); no changes were evident in the cuffed arm. Neither acute nor chronic shear manipulation during exercise influenced endothelium-independent glyceryl trinitrate responses. These results demonstrate that exercise-induced changes in shear provide the principal physiological stimulus to adaptation in flow-mediated endothelial function and vascular remodeling in response to exercise training in healthy humans.

Serum ADMA concentration – an independent factor determining FMD impairment in cardiac syndrome X

Mechanisms of decreased endogenous vascular reactivity in individuals with cardiac syndrome X (CSX) are not fully understood.Aim. To evaluate the following serum markers: total nitric oxide (NO), asymmetric dimethylarginine (ADMA), platelet-derived growth factor (PDGF), and to establish their relation to ultrasound indexes of endothelial function and structural remodeling in CSX patients.Method. The study group consisted of 43 CSX patients (mean age: 56.3 ± 9 years), while the control group included 21 healthy subjects (mean age: 54.86 ± 6.9 years). The high-resolution ultrasound was performed to measure: flow-mediated vasodilatation (FMD), nitroglycerine-mediated vasodilatation (NMD) and intima-media thickness (IMT) of carotid arteries.Results. In CSX patients, significantly lower FMD (9.06 ± 3.2%) and significantly higher IMT (0.667 ± 0.14 mm) values were observed compared to healthy individuals (17.42 ± 8.4%, 0.571 ± 0.2 mm; P < 0.05). Mean total NO serum concentration was significantly higher in the CSX group (48.2 ± 18.2 μmol/L) as compared to controls (32.1 ± 1.4 μmol/L; P < 0.0001). There were no differences in serum ADMA and PDGF levels. In CSX patients, FMD values correlated with NO (r = 0.323; P = 0.039) and ADMA (r = -0.387; P = 0.012) serum levels; however, there were no significant correlations between NO and ADMA concentrations.Conclusion. Serum ADMA concentration is the only independent factor determining FMD impairment.

Associations of Endothelial Function and Air Temperature in Diabetic Individuals

ISEE-0194 Background and Objective: Epidemiological studies consistently show that air temperature is associated with changes in cardiovascular morbidity and mortality. However, the biological mechanisms underlying the association remain largely unknown. As one index of endothelial function, flow-mediated dilatation (FMD) can be viewed as a “barometer” of vascular health. Therefore, the purpose of this study was to analyze the short-term effects air temperature on markers of endothelial function in diabetic patients. Methods: A prospective panel study was conducted on 22 people with diabetes in Chapel Hill, NC, from Nov 2004-Dec 2005. Each subject was studied for four consecutive days. Daily measurements of meteorological data were acquired from the rooftop of the patient exam site. FMD measured by brachial artery ultrasound as well as blood markers on endothelial function were assessed during each patient visit. Data were analyzed using random effects models adjusting for relative humidity, barometric pressure, and particles with an aerodynamic diameter <2.5μm, and day of the week. Results: FMD decreased in association with a 1°C decrease in temperature on the same day (percent-change in mean level:−4.2% with 95%-confidence interval (CI): [−6.9%; −1.4%]) as well as with a delay of one day (−3.3%; 95%-CI: [−6.5%; −0.1%]), four days (−3.4%; 95%-CI: [−6.3%; −0.5%]) and with the 5-day-average (−4.3%; 95%-CI: [−8.4%; −0.3%]). We also found an increase in intercellular adhesion molecules sICAM-1 in association with the 5-day-average of temperature (7.9%; 95%-CI: [2.0%; 13.8%]). A similar trend was seen for vascular cell adhesion molecules sVCAM-1. Other blood markers representing endothelial function such as von Willebrand factor and endothelial-leukocyte adhesion molecule E-selectin did not show any temperature effect. Conclusion: These data suggest that endothelial function is associated with short-term temperature changes. Endothelial dysfunction might contribute to the increase in cardiovascular morbidity and mortality associated with cold weather. This abstract of a proposed presentation does not necessarily represent EPA policy.

Effect of Chronic Sildenafil Treatment on Penile Endothelial Function: A Randomized, Double-Blind, Placebo Controlled Study

Although the effect of phosphodiesterase type 5 inhibitors on endothelial function in the systemic circulation has been extensively studied, its effect on penile endothelial function remains unexplored. Therefore, we evaluated the effect of daily sildenafil on penile endothelial function. A total of 60 patients with erectile dysfunction were randomized blindly to daily placebo or 50 mg sildenafil for 4 weeks. Penile and forearm blood flow as well as endothelial function indices were measured at baseline and after 4 weeks using venoocclusive strain gauge plethysmography for both organs. Sequential changes in flow, maximal blood flow and area under the curve induced by reactive hyperemia after 5 minutes of transient ischemia were considered indices of endothelial function. There were 34 patients treated with sildenafil and 19 on placebo who completed the study. The general characteristics of both groups were comparable. Mean +/- SEM baseline penile blood flow was 6.2 +/- 1.4 and 7.0 +/- 0.6 ml/dl per minute for the placebo and sildenafil groups, respectively (p = 0.54). Baseline forearm blood flow was similar in both groups. At baseline penile AUC was 420 +/- 50 and 520 +/- 50 (p = 0.18), and in the forearm it was 445 +/- 40 and 410 +/- 40 (p = 0.45) for the placebo and sildenafil groups, respectively. After 4 weeks on the assigned drug penile blood flow increased to 11.2 +/- 2 ml/dl per minute in the sildenafil group (p = 0.02) and remained unchanged in the placebo group. After 4 weeks penile AUC increased to 720 +/- 65 in the sildenafil group (0.04) and remained unchanged in the placebo group. Placebo and sildenafil did not affect the indices of forearm endothelial function. Daily sildenafil significantly improves penile blood flow and penile endothelial function indices without causing any relevant systemic effects.

DASH lowers blood pressure in obese hypertensives beyond potassium, magnesium and fibre.

The mechanism underlying blood pressure reduction in the high fruits and vegetables arm of the Dietary Approaches to Stop Hypertension (DASH) Study is unknown but may include potassium, magnesium and fiber. This study was designed to separate minerals and fiber from other components of DASH on blood pressure in abdominally obese metabolic syndrome subjects with prehypertension to Stage 1 hypertension (obese hypertensives). Fifteen obese hypertensives and 15 lean normotensives were studied on a standardized usual diet, randomized to DASH or usual diet supplemented with potassium, magnesium and fiber to match DASH, then crossed over to the complementary diet. All diets were three weeks long, isocaloric and matched for sodium and calcium. In obese hypertensives, blood pressure was lower after 3 weeks on DASH than usual diet (-7.6±1.4/-5.3±1.4 mmHg, p<0.001/0.02 and usual diet supplemented (-6.2±1.4/-3.7±1.4 p<0.005/0.06), whereas blood pressure was not significantly different on usual and supplemented diets. Blood pressure values were not different among the three diets in lean normotensives. Small artery elasticity was lower in obese hypertensives than lean normotensives on the usual and supplemented diets (p<0.02). This index of endothelial function improved in obese hypertensives (p<0.02) but not lean normotensives on DASH and was no longer different from values in lean normotensives (p>0.50). DASH is more effective than potassium, magnesium, and fiber supplements for lowering blood pressure in obese hypertensives, which suggest that high fruits and vegetables DASH lowers blood pressure and improves endothelial function in this group by nutritional factors in addition to potassium, magnesium and fiber.

Acute probucol treatment partially restores vasomotor activity and abnormal lipid metabolism whereas morphological changes are not affected in aorta from long-term STZ-diabetic rats.

The effects of acute probucol treatment on plasma lipids, lipid peroxides and vasomotor activity and structure of aorta were investigated in long-term streptozotocin (STZ)-diabetic rats. Treatment with probucol (300 mg/kg/day, i.o.) was initiated 10 weeks after the induction of diabetes and was continued for 2 or 3 weeks. Plasma cholesterol, triglyceride and thiobarbituric acid reactive substance (TBARS) levels were markedly increased in untreated diabetic rats, however, probucol treatment led to significant reductions in all of these characteristics in diabetic animals. Plasma glucose and insulin levels were similar between untreated and probucol-treated diabetic groups. STZ-diabetes impaired morphological integrity of aorta and caused significantly increase in contractile response to noradrenaline (NA). The percentage of endothelial response (PER), which was calculated in terms of the NA-induced maximum contractile response of aorta, as index of endothelial function, significantly decreased in untreated diabetic rats. Treatment of diabetic rats with probucol resulted in partial restorations in endothelial function and NA-induced contraction in aorta, whereas morphological changes were not affected. These observations suggest that the ability of acute probucol treatment to restore vessel functions may have important implications regarding the pathogenesis and treatment of diabetes and its complications.

Cardio-respiratory Fitness Affects Glucose Control And Thus Cardiovascular Disease Risk In Postmenopausal Women.

Increased glucose levels above a threshold of 4.9 mmol/L are associated with a greater risk of cardiovascular disease (CVD). The menopause has been associated with impaired glucose control, including poor glucose tolerance, increased glycosylated haemoglobin (HbA1C) and fasting insulin concentration. The positive effect of increased cardio-respiratory fitness (CRF) upon glucose control in postmenopausal women (PM-women) is unclear. PURPOSE: To determine the effects of CRF upon glucose control in PM-women. METHODS: CRF was assessed via Bruce treadmill test in 79 sedentary-to-moderately active and 10 marathon running (MR) PM-women. Sedentary-to-moderately active women were classified into low, medium or high CRF levels according to VO2 peak, MR were a separate group. Assessment of glucose control included analysis of fasting venous glucose and insulin (thus the homeostasis model assessment (HOMA)) and HbA1c concentrations The following additional CVD risk factors were assessed: body composition (skinfold analysis/waist and hip circumferences, BMI and body mass), flow mediated dilation (reactive hyperaemia) as an index of endothelial function, total cholesterol, high and low density lipoproteins, triglycerides and high sensitivity C-reactive protein (hsCRP). CRF level differences in glucose control variables were analysed via ANCOVA (all other variables as covariates), and multiple regression assessed which variables best predicted glucose control variables. RESULTS: Fasting plasma glucose concentration was the only glucose control variable to differ between CRF levels with the MR group having significantly lower concentrations (4.1mmol/L) than all other CRF levels (low CRF 5.7; medium CRF 5.5; high CRF 5.5 mmol/L). Additionally, MR women were the only group to have a glucose concentration less that 4.9 mmol/L (threshold for CVD risk). CRF was found to be the strongest predictor for glucose concentration. Conversely, body mass, waist circumference and hsCRP were the strongest predictors of insulin concentration and HOMA, whereas CRF had little predictive influence. CONCLUSION: Very high levels of CRF similar to marathon runners may be required to lower glucose concentration in PM-women to levels below the threshold for increased risk of CVD. Supported by a Heart Research UK grant 2508/06/08

Retrograde Flow and Shear Rate Acutely Impair Endothelial Function in Humans

Changes in arterial shear stress induce functional and structural vasculature adaptations. Recent studies indicate that substantial retrograde flow and shear can occur through human conduit arteries. In animals, retrograde shear is associated with atherogenic effects. The aim of this study was to examine the impact of incremental levels of retrograde shear on endothelial function in vivo. On 3 separate days, we examined bilateral brachial artery flow-mediated dilation, an index of NO-mediated endothelial function, in healthy men (24+/-3 years) before and after a 30-minute intervention consisting of cuff inflation to 25, 50, or 75 mm Hg. Cuff inflations resulted in "dose"-dependent increases in retrograde shear rate, compared with the noncuffed arm, within subjects (P<0.001). Flow-mediated dilation in the cuffed arm did not change in response to the 25-mm Hg stimulus but decreased significantly after both the 50- and 75-mm Hg interventions (P<0.05). The decrease in flow-mediated dilation after the 75-mm Hg intervention was significantly larger than that observed after a 50-mm Hg intervention (P=0.03). In the noncuffed arm, no changes in shear rate or flow-mediated dilation were observed. These results demonstrate that an increase in retrograde shear rate induces a dose-dependent attenuation of endothelial function in humans. This finding contributes to our understanding regarding the possible detrimental effects of retrograde shear rate in vivo.