Endothelium-dependent Flow-mediated Vasodilation Research Articles

Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependent vasoreactivity.

Abnormalities in endothelial function may be associated with increased cardiovascular risk in diabetic patients. We examined the effect of an oleic-acid-rich diet on insulin resistance and endothelium-dependent vasoreactivity in type 2 diabetes. Eleven type 2 diabetic patients were changed from their usual linoleic-acid-rich diet and treated for 2 months with an oleic-acid-rich diet. Insulin-mediated glucose transport was measured in isolated adipocytes. Fatty acid composition of the adipocyte membranes was determined by gas-liquid chromatography and flow-mediated endothelium-dependent and -independent vasodilatation were measured in the superficial femoral artery at the end of each dietary period. There was a significant increase in oleic acid and a decrease in linoleic acid on the oleic-acid-rich diet (p<0.0001). Diabetic control was not different between the diets, but there was a small but significant decrease in fasting glucose/insulin on the oleic-acid-rich diet. Insulin-stimulated (1 ng/ml) glucose transport was significantly greater on the oleic- acid-rich diet (0.56+/-0.17 vs. 0.29+/-0.14 nmol/10(5) cells/3 min, p<0.0001). Endothelium-dependent flow-mediated vasodilatation (FMD) was significantly greater on the oleic-acid-rich diet (3.90+/-0.97% vs. 6.12+/-1.36% p<0.0001). There was a significant correlation between adipocyte membrane oleic/linoleic acid and insulin-mediated glucose transport (p<0.001) but no relationship between insulin-stimulated glucose transport and change in endothelium-dependent FMD. There was a significant positive correlation between adipocyte membrane oleic/linoleic acid and endothelium-dependent FMD (r=0.61, p<0.001). Change from polyunsaturated to monounsaturated diet in type 2 diabetes reduced insulin resistance and restored endothelium-dependent vasodilatation, suggesting an explanation for the anti-atherogenic benefits of a Mediterranean-type diet.

Effect of short-term vitamin (folic acid, vitamins B 6 and B 12) administration on endothelial dysfunction induced by post-Methionine load hyperhomocysteinemia

This study showed that short-term vitamin administration effectively reduced post-methionine load homocysteine levels and thereby ameliorated endothelium-dependent flow-mediated vasodilation in 16 healthy adults. Post-methionine load homocysteine levels decreased from 22.7+/-3.8 to 17.0+/-2.1 micromol/L (p <0.001), and flow-mediated vasodilation after methionine load increased from 8.6+/-3.6% to 13.8+/-2.9% (p <0.001) after vitamin administration.

Endothelium-dependent flow-mediated vasodilation in the postprandial state in type 2 diabetes mellitus

This study examined the effects of fat- plus sucrose-rich meals on endothelium-dependent flow-mediated vasodilation in diabetic patients. Flow-mediated vasodilation in the postprandial state decreased significantly, and the decrease correlated inversely with the magnitude of postprandial hyperglycemia, suggesting that endothelial function in diabetic patients becomes impaired postprandially.

Plasma Homocysteine Is Weakly Correlated with Plasma Endothelin and von Willebrand Factor but not with Endothelium-dependent Vasodilatation in Healthy Postmenopausal Women

Hyperhomocysteinemia is an independent cardiovascular risk factor, possibly through the induction of endothelial dysfunction. The postmenopausal state is associated with increased plasma homocysteine. We examined whether increased homocysteine is associated with impaired endothelial function. Sixty-three hysterectomized but otherwise healthy postmenopausal women (54.8 +/- 3.5 years) participated in this study. Fasting total plasma homocysteine (tHcy) was measured as free plus protein-bound homocysteine. Endothelial function was assessed by measuring plasma concentrations of the endothelium-derived proteins endothelin (ET), von Willebrand factor (vWF), and plasminogen activator inhibitor type 1 (PAI-1) as well as brachial artery flow-mediated, endothelium-dependent vasodilatation (FMD). Plasma tHcy was 9.6 +/- 2.5 micromol/L. After adjustment for possible confounders, a 1 micromol/L increase in tHcy was associated with an increase in ET of 0.08 ng/L (P = 0.045) and an increase in vWF of 4.2% (P = 0.05). No statistically significant association was present between tHcy and PAI-1 or FMD. Increased fasting homocysteine in postmenopausal women may impair some aspects of endothelial function. It is of clinical interest to study whether homocysteine lowering can improve endothelial function and thus cardiovascular morbidity and mortality in postmenopausal women.

Effect of prolonged administration of transdermal estradiol on flow-mediated endothelium-dependent and endothelium-independent vasodilation in healthy postmenopausal women

In 15 postmenopausal women with no cardiovascular risk factors, hormone replacement with transdermal estradiol (50 microg/day for 2 months) did not enhance flow-mediated endothelium-dependent vasodilation, reduce endothelium-independent vasodilation, and did not modify the pulsatility index and blood flow of the brachial artery. The present data do not support a positive effect of replacement with transdermal estradiol on vessel vasodilation in healthy, postmenopausal women.

Hyperglycemia rapidly suppresses flow-mediated endothelium- dependent vasodilation of brachial artery

OBJECTIVESWe examined whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading.BACKGROUNDEndothelial dysfunction has been shown to occur in patients with diabetes mellitus (DM), and chronic hyperglycemia is implicated as a cause of endothelial dysfunction. However, in many patients with Type 2 DM and in those with impaired glucose tolerance (IGT), fasting blood glucose may be within normal limits, and hyperglycemia occurred only post-prandially.METHODSWith ultrasound technique, we measured flow-mediated endothelium-dependent vasodilation during oral glucose tolerance test in 58 subjects: (17 patients with normal glucose tolerance [NGT], 24 with IGT, and 17 with type 2 DM). In addition, we measured the levels of thiobarbituric acid reactive substances (TBARS) and nitrite/nitrate.RESULTSFlow-mediated vasodilation decreased after glucose loading (NGT: 7.53 ± 0.40, 4.24 ± 0.28 and 6.35 ± 0.40, in fasting, at 1- and 2-h, respectively, IGT: 6.50 ± 0.48, 1.40 ± 0.41∗∗ and 4.00 ± 0.47∗, respectively; DM: 4.77 ± 0.37, 1.35 ± 0.38∗∗ and 1.29 ± 0.29%∗∗, respectively; ∗p < 0.01 vs. fasting, ∗∗p < 0.005 vs. fasting). The TBARS concentration increased in parallel with plasma glucose level in each group (NGT: 1.43 ± 0.07, 2.03 ± 0.12 and 1.80 ± 0.12, respectively; IGT: 1.65 ± 0.11, 2.46 ± 0.12∗∗ and 1.94 ± 0.08∗, respectively; DM: 1.73 ± 0.07, 2.34 ± 0.08∗∗ and 2.47 ± 0.09∗∗ nmol/ml, respectively; ∗p < 0.05 vs. fasting, ∗∗p < 0.01 vs. fasting). Glucose loading did not change nitrite/nitrate concentration in any of the groups.CONCLUSIONSHyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent vasodilation, probably through increased production of oxygen-derived free radicals. These findings strongly suggest that prolonged and repeated post-prandial hyperglycemia may play an important role in the development and progression of atherosclerosis.

Normal pregnancy is associated with enhanced endothelium-dependent flow-mediated vasodilation.

Normal pregnancy is characterized by reduced systemic vascular resistance, which may be mediated by nitric oxide (NO). We compared endothelial vasomotor function in 71 normal pregnant women (13 in first, 29 in middle, and 29 in last trimester) to 37 healthy age-matched controls. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia [with increased flow causing endothelium-dependent dilation (FMD)], and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with controls, resting flow and brachial artery diameter were significantly higher during the middle and last trimesters. Reactive hyperemia was reduced in all pregnant groups. FMD increased from the first trimester (by 26%), reaching the highest value in the last trimester (to 47% above nonpregnant values). FMD was significantly correlated to pregnancy status (nonpregnant or pregnant) and to vessel size. Nitroglycerin-induced dilation was similar in pregnant and nonpregnant women. A longitudinal study of eight women evaluated in the first, middle, and last trimesters confirmed an increase in FMD throughout pregnancy. The study supports the idea that basal and stimulated NO activity is enhanced in normal pregnancy and may contribute to the decrease in peripheral resistance.

Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition: A potential role of bradykinin

OBJECTIVESThis study was performed to determine whether angiotensin converting enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation in patients with atherosclerosis or its risk factors and whether this is mediated by enhanced bradykinin activity.BACKGROUNDAbnormal coronary vasomotion due to endothelial dysfunction contributes to myocardial ischemia in patients with atherosclerosis, and its reversal may have an antiischemic action. Previous studies have shown that ACE inhibition improves coronary endothelial responses to acetylcholine, but whether this is accompanied by improved responses to shear stress remains unknown.METHODSIn 19 patients with mild atherosclerosis, metabolic vasodilation was assessed during cardiac pacing. Pacing was repeated during separate intracoronary infusions of low-dose bradykinin (BK) and enalaprilat. Endothelium-dependent and -independent vasodilation was estimated with intracoronary BK and sodium nitroprusside respectively.RESULTSEnalaprilat did not alter either resting coronary vascular tone or dilation with sodium nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that constricted abnormally with pacing (−5 ± 1%) dilated (3 ± 2%) with pacing in the presence of enalaprilat (p = 0.002). Similarly, BK at a concentration (62.5 ng/min) that did not alter resting diameter in the constricting segments also improved the abnormal response to a 6 ± 1% dilation (p < 0.001). Cardiac pacing-induced reduction in coronary vascular resistance of 27 ± 4% (p < 0.001) remained unchanged after enalaprilat.CONCLUSIONSThus ACE inhibition: A) selectively improved endothelium-dependent but not -independent dilation, and B) abolished abnormal flow-mediated epicardial vasomotion in patients with endothelial dysfunction, in part, by increasing endogenous BK activity.

The Short-and Long-Term Effects of Gingko Biloba Extracts on the Endothelial Function in Patients with Coronary Artery Disease

Background:The gingko biloba extracts (GBE are known to inducing vasodilation by increasing NO or PGI 2. However, the effects on the endothelial function and clinical symptoms of patients with coronary artery disease (CAD are not clear. Methods: The flow-mediated endothelium-dependent brachial artery vasodilation using high-resolution ultrasound was measured before and 2 hours after intake of GBE (120 mg single PO and 1 month after regular intake of GBE (80 mg bid PO in 33 patients (mean;60 yrs, 26 males with CAD who had been diagnosed by coronary angiogram and managed with medication for more than 1 month. Results: The only one patient could not continue to take GBE due to severe nausea. The frequency or severity of chest pain was decreased in 31 patients among the other 32 patients. The flow-mediated brachial artery vasodilation (mean±SD were significantly (p<0.001 improved from 8.9±3.9% before to 13.4±4.5% and 13.7±4.0% 2 ho- urs and 1 month after taking GBE, respectively. The brachial artery diameter was increased from 4.42±0.67 mm before to 4.45±0.66 mm and 4.64±0.60 (p<0.005 after taking GBE, respectively. The endothelial function in patients with diabetes mellitus (5 from 33 was not improved 2 hours after taking GBE, but improved 1 month after GBE. The improvement of endothelial dysfunction in patients with hyperlipidemia or hypertension was less than patients without it. Conclusion:GBE has favorable short- and long-term effects on the endo-thelial function and clinical symptoms as well as long-term vasodilatation in patients with CAD without serious side effects. ( ( ( (Korean Circulation J 1999;29( ( ( (2 :919-927

Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease

Previous studies showed a weak correlation between endothelial function of the coronary arteries as assessed by acetylcholine and brachial artery vasomotion during reactive hyperemia. When the same stimulus was used, we obtained a strong correlation between flow-mediated dilation in the coronary and brachial arteries (r=0.78, p <0.001), so that noninvasive assessment of flow-mediated dilation in the brachial artery could be used as a surrogate measure for coronary artery endothelial function.

Regional differences in endothelial function in horse lungs: possible role in blood flow distribution?

We investigated regional differences of in vitro responses of pulmonary arteries (6-mm OD) from the dorsocaudal (top) and cranioventral (bottom) lung regions to endothelium-dependent vasodilators (methacholine, bradykinin, and calcium ionophore A-23187). Methacholine relaxed endothelium-intact top vessels; however, in bottom vessels, a small relaxation preceded a profound contraction. In top vessels, removal of endothelial cells converted relaxation to contraction, and in bottom vessels it abolished relaxation and enhanced contraction. Bradykinin and A-23187 were more potent and caused greater endothelium-mediated relaxation in top than in bottom arteries. The endothelium-independent vasodilator sodium nitroprusside caused similar relaxations in all rings. Nomega-nitro-L-arginine and NG-monomethyl-L-arginine and methylene blue abolished relaxation of top and bottom arteries to methacholine; meclofenamate had little effect. We conclude that regional differences in endothelium-mediated relaxation are caused by differences in the magnitude of the endothelial release of nitric oxide. Similar differences in endothelium-dependent flow-mediated vasodilation and endothelial nitric oxide release may result in preferential perfusion of caudodorsal lung regions.

The impairment of flow-mediated vasodilatation in obese men with visceral fat accumulation.

Obesity has been reported to be associated with coronary artery disease and other atherosclerotic diseases. Recently, evidence has accumulated indicating that intra-abdominal visceral fat accumulation contributes to atherogenesis; however, the mechanism underlying this remains to be determined. This study was undertaken to elucidate whether intra-abdominal visceral fat accumulation impairs vascular endothelial function in obese men. Thirty-eight obese men (body mass index (BMI) > or = 26.0), aged 19-64 y (mean age 37.6 +/- 1.8 y) and 23 age-matched non-obese subjects were examined. According to the ratio of the maximum thickness of preperitoneal fat to the minimum thickness of subcutaneous fat (Pmax/Smin) obtained by longitudinal ultrasound scanning in the subxiphoid region in obese men, we divided obese subjects into two categories; visceral (Pmax/Smin > or = 1; n=23) and subcutaneous type (Pmax/Smin < 1; n=15). To investigate endothelial function, we performed ultrasound measurement of the brachial artery diameter non-invasively both at rest and during reactive hyperaemia in the muscle distal to the brachial artery which causes endothelium-dependent vasodilatation. The brachial diameter change was also measured after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. Flow-mediated diameter (D) increase (%FMD; deltaD/D x 100), in the subjects with visceral type obesity (3.09 +/- 0.43%) was significantly lower than those of the subjects with subcutaneous type obesity and non-obese subjects (7.90 +/- 0.51%, 8.91 +/- 0.44%, respectively, P < 0.01). The magnitude of endothelium-independent vasodilatation by nitroglycerin was similar in all groups. On multiple regression analysis, the Pmax/Smin showed a significant inverse correlation with %FMD. The subjects with visceral type obesity, rather than those with the subcutaneous type, are associated with impaired flow-mediated endothelium-dependent vasodilatation of the brachial artery.

Noninvasive assessment of endothelium-dependent flow-mediated dilation of the brachial artery.

Coronary atherosclerosis is characterized by an early loss of endothelium-dependent vasodilation. However, the methods of assessing coronary endothelial function are invasive and difficult to repeat over time. Recently, a noninvasive ultrasound method has been widely used to measure flow-mediated dilation in the brachial artery as a surrogate test for endothelial function. We seek to further validate this method of measuring vascular function. The brachial artery diameters and blood flow of 20 normal volunteers (10 males and 10 females) were measured using high resolution (7.5 MHz) ultrasound and strain gauge plethysmography. Flow-mediated endothelium-dependent vasodilation was measured in the brachial artery during reactive hyperemia after 5 minutes of cuff occlusion in the upper arm. The brachial artery diameter increased maximally by 9.7 +/- 4.3% from baseline at 1 min after cuff release and blood flow increased by 1002 +/- 376%. Five min of cuff occlusion was sufficient to achieve 97 +/- 6% of maximal brachial artery dilation and degree of dilation was not different whether the cuff was inflated proximally or distally to the image site. The intraobserver variability in measuring brachial diameters was 2.9% and the variability of the hyperemic response was 1.4%. In young, healthy men and women, the baseline brachial artery diameter was the only factor that was predictive of the flow-mediated vasodilation response. The brachial noninvasive technique has been further validated by the determination of flow-mediated dilation. This method of assessing endothelial function may help to determine the importance of vasodilator dysfunction as a risk factor in the development of atherosclerosis.

Frequency of systemic microvascular dysfunction in syndrome X and in variant angina

In addition to coronary vascular abnormalities, patients with syndrome X and variant angina often have systemic vascular symptoms. To determine whether these patients exhibit a generalized abnormality of vasoreactivity, we used high-resolution ultrasound to compare flow responses and endothelial function in the brachial artery in 21 patients with syndrome X, 15 patients with variant angina, and 20 healthy controls. Arterial diameter was measured at rest, after reactive hyperemia (endothelium-dependent flow-mediated vasodilation), and after sublingual glyceryl trinitrate (endothelium-independent vasodilation). The magnitude of hyperemic flow response was measured after transient forearm occlusion. Flow-mediated dilation in the brachial artery did not differ among patients with syndrome X, variant angina, and controls (2.7 ± 2.3%, 3.8 ± 3.5%, and 4.2 ± 3.0%). Endothelium-independent vasodilation in the brachial artery was similar in the 3 groups (16.0 ± 7.2%, 12.7 ± 4.6%, and 14.8 ± 4.9%). Despite a considerable overlap, reactive hyperemia was lower in patients with syndrome X than in patients with variant angina and controls (342 ± 86% vs 466 ± 184% and 452 ± 104%; p <0.05). These findings indicate that a substantial proportion of patients with syndrome X have a systemic microvascular abnormality, whereas variant angina is predominantly a segmental disorder of conduit vessels.

Modulation of Endothelium-Dependent Flow-Mediated Dilatation of the Brachial Artery by Sex and Menstrual Cycle

Estrogen has been reported to augment endothelium-dependent vasodilatation. The role of endogenous ovarian hormones in modulating endothelium-dependent vasodilatation, however, remains to be determined. The purpose of the present study was to investigate the effects of sex and menstrual cycle on endothelium-dependent flow-mediated vasodilatation. Seventeen female volunteers 25.1 +/- 0.8 years old and 17 age-matched male volunteers were examined. We measured brachial artery diameters noninvasively using a 7.5-MHz ultrasound machine at rest, during reactive hyperemia, and after sublingual nitroglycerin administration. All female subjects were studied three times each, in three different phases of one menstrual cycle (M, menstrual phase; F, follicular phase; and L, luteal phase). Flow-mediated diameter (D) increase (%FMD; delta D/D x 100) in M, when serum estradiol level was low (121.9 +/- 12.5 pmol/L), was 11.22 +/- 0.58%, and the value was comparable to that in male subjects (10.60 +/- 0.75%). %FMD increased in F (18.20 +/- 0.81%, P < .01 versus M) and L (17.53 +/- 0.74%, P < .01 versus M), when serum estradiol level was high (F, 632.0 +/- 74.5 and L, 533.8 +/- 33.4 pmol/L, P < .01 versus M). Endothelium-independent vasodilatation by nitroglycerin increased in both F and L. However, the increment was smaller than that of %FMD. Endothelium-dependent vasodilatation varies during the menstrual cycle. The endogenous estradiol may be involved in this menstrual cycle-related vasodilatation.

Estrogen Improves Endothelium-Dependent, Flow-Mediated Vasodilation in Postmenopausal Women

To assess the effect of estrogen replacement therapy on endothelium-dependent vasodilation in postmenopausal women. Double-blind, placebo-controlled, crossover trial. University medical center. 13 postmenopausal women aged 44 to 69 years (average age, 55 +/- 7 years). Patients were randomly assigned to receive placebo, oral estradiol at a dose of 1 mg/d, and oral estradiol at a dose of 2 mg/d. Each treatment phase lasted 9 weeks. High-resolution ultrasonography was used to measure vascular reactivity in a peripheral conduit vessel, the brachial artery. Endothelium-dependent vasodilation was determined by measuring the change in brachial artery diameter during increases in flow induced by reactive hyperemia. Endothelium-independent vasodilation was measured after sublingual nitroglycerin was administered. Flow-mediated, endothelium-dependent vasodilation of the brachial artery was greater when patients received estradiol (13.5% and 11.6% for 1-mg and 2-mg doses, respectively) than when patients received placebo (6.8%; P < 0.05 for each dose compared with placebo). In contrast, estrogen administration had no effect on endothelium-independent vasodilation as assessed by sublingual nitroglycerin. Short-term estrogen replacement therapy improves flow-mediated endothelium-dependent vasodilation in postmenopausal women. This improvement may be mediated by a direct effect of estrogen on vascular function or may be induced through modification of lipoprotein metabolism.

Flow stimulates endothelial cells to release a nitrovasodilator that is potentiated by reduced thiol

We designed a novel system to study flow-mediated endothelium-dependent vasodilation. Vascular rings of rabbit thoracic aorta were mounted for isometric tension recording in a flow chamber filled with physiological saline solution. The flow chamber contained a stir bar and was mounted on a magnetic stirrer to induce vortical flow. Norepinephrine (NE, 10(-6) M) induced contraction of the vascular rings. Bovine endothelial cells on microcarrier beads added to the chamber had little effect on contraction to NE in the absence of flow. Flow induced endothelium-dependent relaxation of the vascular rings that was dependent on the flow rate. Relaxations were annulled or reversed to a contraction with methylene blue, bovine hemoglobin, or N-monomethyl-L-arginine. Conversely, N-acetyl-L-cysteine augmented the flow-mediated relaxation. Furthermore, in the presence of N-acetyl-L-cysteine, the half-life of the endothelium-dependent relaxing factor was increased. In conclusion, the stimulus of flow induces the release by endothelial cells of a diffusible, short-lived factor with the attributes of a nitrovasodilator. The action of this endogenous vasodilator is augmented by the reduced thiol N-acetyl-L-cysteine.

Comparing the Influence of Hyperglycemia on Flow Mediated Endothelium-dependent Vasodilation between Healthy Males of Average Fitness and Endurance Athletes

Endothelial dysfunction has been determined to be an indicator of atherosclerosis, an early stage in the development of cardiovascular disease. To detect potential endothelial dysfunction, the use of flow-mediated dilation (FMD) techniques, like reactive hyperemia (RH), is widely used in this area of research. An artery experiences FMD when there is an increase in blood velocity, resulting in an increase in the shear stress on the endothelium of the artery. In response to this, the artery’s endothelium will release compounds to vasodilate the artery. A growing body of research has found that a hyperglycemic state, through the ingestion of glucose, may hinder the endothelium’s ability to vasodilate in response to an increase in shear stress, thus leading to transient dysfunction of the artery. Furthermore, research is also exploring ways to attenuate this decrease in dilation. For example, one study has found that the use of exercise after ingesting glucose will attenuate this decrease in FMD response. However, research has not yet explored the relationship between fitness level and FMD in a hyperglycemic state. As a result, the purpose of this study is to compare the FMD response in sedentary participants to active participants during hyperglycemia.