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Results for “Endothelial function”

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PubMed1999

[Effect of tongxinluo capsule in treating variant angina pectoris patients and its influence on endothelial function].

OBJECTIVE: To assess the efficacy of Tongxinluo capsule (TXLC) in treating variant angina pectoris and its effect on endothelial function. METHODS: Sixty-four patients with variant angina pectoris were enrolled in the study for four weeks by a randomized clinical trial treatment with TXLC or isosorbide mononitrate. RESULTS: (1) The symptoms of both groups were significantly improved, the total effective rate of TXLC and isosorbide were 86.67% and 87.10% respectively; (2) The level of serum nitric oxide was increased, and the serum endothelin was decreased after treatment, there was no significant difference between these two groups. CONCLUSION: TXLC could effectively improve the symptoms of variant angina pectoris, the mechanism of which may likely be mediated by nitric oxide and endothelin.

Adult↗

PubMed2001

Alcohol and endothelial function: a brief review.

1. In spite of the dose-related effects of alcohol consumption to increase blood pressure, regular light to moderate alcohol intake appears to confer protection against both coronary artery disease and ischaemic stroke. In contrast, heavy alcohol consumption increases the risk of coronary artery disease and the risk of both haemorrhagic and ischaemic stroke. 2. Effects of alcohol consumption on endothelial cell function may be relevant to these disparate effects on cardiovascular outcomes. In in vitro animal studies, low doses of alcohol have been demonstrated to increase release of nitric oxide and augment endothelium-mediated vasodilatation, whereas higher doses impair endothelium-dependent relaxation responses. In contrast, chronic administration of alcohol to rats has generally been associated with tolerance to the acute inhibitory effects of alcohol on endothelium-mediated vasodilatation and may even result in augmentation of such responses. 3. The few human studies to date that have examined the effects of alcohol on endothelial function have focused on postischaemic flow-mediated dilation of the brachial artery (FMD). Although blunted FMD responses have been reported in alcoholic subjects, acute administration of alcohol or short-term interventions to reduce alcohol intake have had no effect to either improve or impair FMD. 4. Further studies in humans assessing acute and longer term dose-related effects of alcohol on endothelial function in both conduit and resistance vessels will be necessary if the relevance of the findings from in vitro and in vivo animal studies are to be understood in the context of the complex interrelationships of alcohol with cardiovascular disease.

Alcohol Drinking↗

PubMed1999

Oral folate enhances endothelial function in hyperhomocysteinaemic subjects.

BACKGROUND: Elevated plasma homocysteine (Hcy) is a risk factor for vascular disease. A postulated mechanism is vascular endothelial damage by homocysteine. Hcy levels are inversely related to blood concentrations of folate and can be lowered by folate supplements. The effect of oral folic acid on endothelial function was investigated in healthy adults with mild hyperhomocysteinaemia. PATIENTS AND METHODS: Eighteen healthy subjects (Hcy > 13 micromol L-1 at entry), from a screening population of 890 volunteers, were entered into a randomised double-blind placebo-controlled crossover study of oral folic acid (5 mg daily for six weeks) with a six week interval between treatments. Flow-mediated (endothelium-dependent) and (endothelial-independent) glyceryl trinitrate (GTN)-mediated brachial artery dilatation were measured by high resolution wall tracking. RESULTS: Folate supplementation enhanced endothelium-dependent responses (+0.08 +/- 0.05 vs. +0.04 +/- 0.04 mm, P = 0.015) but endothelium-independent responses (GTN) were unchanged. Folate reduced Hcy (8.7 +/- 2.5 vs. 12.1 +/- 3.6 micromol L-1). CONCLUSION: High dose folic acid supplementation enhances endothelium-dependent vascular function and lowers plasma Hcy. This provides preliminary evidence that folate may have beneficial cardiovascular effects in adults with mild hyperhomocysteinaemia.

Administration, Oral↗

PubMed2004

Endothelial function and mechanical properties of the common carotid artery in children on parenteral nutrition.

Intravenous administration of nutrition mixtures induces endothelial damage and arterial wall remodeling in animal models. To study endothelial function and common carotid artery mechanical properties in children receiving parenteral nutrition, we used noninvasive ultrasonic measurements in 18 children on parenteral nutrition and 18 controls. No difference appeared in the geometry of the common carotid artery (intima media thickness, systolic and diastolic diameters) between the patients on parenteral nutrition and the controls. The incremental elastic modulus was significantly higher in the patients on parenteral nutrition (1.8 +/- 0.4 versus 1.4 +/- 0.5 4 mm Hg x 10(3), p < 0.05) reflecting alteration of the elastic properties of the arterial wall independent of the vessel geometry. The flow-mediated dilatation of the brachial artery was significantly lower in the patients on parenteral nutrition (6 +/- 3 versus 8 +/- 3%, p < 0.05), whereas the dilatation after glyceryl trinitrate administration was similar (22 +/- 9 versus 25 +/- 9%). Children on parenteral nutrition exhibit endothelial dysfunction and altered stiffness of the common carotid artery. The noninvasive methods used in this study may prove useful for objectively determining the effects of various preventive methods.

Adolescent↗

PubMed2005

Ghrelin improves endothelial function in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome importantly accelerates the atherosclerotic process, the earliest event of which is endothelial dysfunction. Ghrelin, a gastric peptide with cardiovascular actions, has been shown to inhibit proatherogenic changes in experimental models. This study therefore investigated whether ghrelin administration might beneficially affect endothelial function in metabolic syndrome. METHODS AND RESULTS: Endothelium-dependent and -independent vasodilator responses to intra-arterial infusion of increasing doses of acetylcholine and sodium nitroprusside (SNP), respectively, were assessed by strain-gauge plethysmography before and after local administration of human ghrelin (200 microg/min). During saline, the vasodilator response to acetylcholine was significantly blunted (P=0.008) in patients with metabolic syndrome (n=12, 5 female) compared with controls (n=12, 7 female), whereas the vasodilator response to SNP was not different between groups (P=0.68). In patients with metabolic syndrome, basal plasma ghrelin was significantly lower than in controls (P=0.02). In these patients, ghrelin infusion markedly increased intravascular concentrations of the peptide (P<0.001) and resulted in a potentiation of the vasodilator response to acetylcholine (P=0.001 versus saline) but not to SNP (P=0.22). This effect was likely related to enhanced nitric oxide bioavailability because, in a group of patients with metabolic syndrome (n=6, 2 female), ghrelin had no effect on the vasodilator response to acetylcholine (P=0.78 versus saline) after nitric oxide inhibition by NG-monomethyl-L-arginine. CONCLUSIONS: These findings indicate that ghrelin reverses endothelial dysfunction in patients with metabolic syndrome by increasing nitric oxide bioactivity, thereby suggesting that decreased circulating levels of the peptide, such as those found in these patients, might play a role in the pathobiology of atherosclerosis.

Acetylcholine↗

PubMed2005

Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease.

BACKGROUND: It has been shown that acute intake of red wine improves endothelial-dependent vasodilatation. It is not clear, however, which constituents of red wine are responsible for this effect. We examined whether acute intake of a red grape polyphenol extract has a positive effect on brachial artery flow-mediated dilatation. METHODS: We recruited 30 male patients with coronary heart disease. They were randomly assigned either to a red grape polyphenol extract (600 mg) dissolved in 20 ml of water (n = 15) or 20 ml of water (placebo) (n = 15). The extract of grapes contained 4.32 mg epicatechin, 2.72 mg catechin, 2.07 mg gallic acid, 0.9 mg trans-resveratrol, 0.47 mg rutin, 0.42 mg epsilon-viniferin, 0.28 mg, p-coumaric acid, 0.14 mg ferulic acid and 0.04 mg quercetin per gram. Flow-mediated dilatation of the brachial artery was evaluated after reactive hyperemia induced by cuff obstruction of the forearm, using high-resolution ultasonography. Particularly, flow-mediated dilatation was measured after fasting and 30, 60 and 120 min after the intake of the grape extract or placebo. RESULTS: Intake of the red grape polyphenol extract caused an increase in flow-mediated dilatation, peaking at 60 min, which was significantly higher than the baseline values (4.52+/-1.34 versus 2.6+/-1.5%; P < 0.001) and the corresponding values at 60 min after the intake of placebo (4.52+/-1.34 versus 2.64+/-1.8%, P < 0.001). There was no change in FMD values after the intake of placebo throughout the whole duration of the study. CONCLUSION: Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease. These results could probably, at least partly, explain the favorable effects of red wine on the cardiovascular system.

Blood Flow Velocity↗

PubMed2005

Endothelin receptor blockade improves endothelial function in atherosclerotic patients on angiotensin converting enzyme inhibition.

OBJECTIVES: Endothelin-1 (ET-1) and angiotensin II may contribute to endothelial dysfunction, which is associated with increased risk of events in patients with coronary artery disease. The objective was to test whether dual ETA/ETB receptor antagonism improves endothelium-dependent vasodilatation (EDV) in atherosclerotic patients, also on treatment with angiotensin converting enzyme (ACE) inhibitor. DESIGN AND SETTING: EDV and endothelium-independent vasodilatation were determined in 37 patients with atherosclerosis during measurement of forearm blood flow (FBF) with venous occlusion plethysmography. The patients were then randomized to treatment with ramipril 10 mg o.d. (n=21) or placebo (n=16) for 3 months in a double-blind fashion. RESULTS: Intra-arterial infusion of the ETA receptor antagonist BQ123 and the ETB receptor antagonist BQ788 (both 10 nmol min(-1)) increased basal FBF by 42 +/- 4% (P <0.001) and enhanced EDV (P <0.001). Following 3 months ramipril treatment, ET receptor blockade still enhanced EDV. Acetylcholine 10 and 30 mg min(-1) increased FBF by 68 +/- 12 and 64 +/- 12 mL min(-1)/1000 mL before vs. 101 +/- 17 and 101 +/- 16 mL min(-1)/1000 mL following ET receptor blockade in the ramipril group (P <0.001). CONCLUSIONS: Dual ETA/ETB receptor blockade improves endothelial function and exerts direct vasodilator effects in patients with atherosclerosis, also on treatment with ramipril suggesting that ET receptor blockade may have important therapeutic effects when added to ACE inhibition in these patients.

Acetylcholine↗

PubMed2006

Testing endothelial function of brachial and cavernous arteries in patients with erectile dysfunction.

INTRODUCTION: There is considerable clinical and scientific evidence that endothelial dysfunction may be an important clinical link connecting erectile dysfunction (ED) with cardiovascular diseases. AIMS: To modify the method of assessment of endothelial function of cavernosal arteries, to develop a new algorithm for evaluating its results, and to investigate the relationship between postocclusive changes in the diameter of brachial and cavernous arteries. METHODS: The study participants were 212 patients presenting to our department complaining of ED and 40 healthy volunteers without sexual problems, which formed the control group. All patients with ED underwent complex evaluation and ultrasound assessment of postocclusive changes in the diameter of cavernosal arteries modified by us and standard ultrasound assessment of endothelium-dependent flow-mediated dilation of the brachial artery. MAIN OUTCOME MEASURES: As the main outcome measure, the percent of increase of the cavernosal arteries diameter (PICAD) was recorded. RESULTS: In the patients with arteriogenic ED, PICAD values were significantly less than in other groups (P < 0.001 for pairs of comparison). At the same time there were no differences between the control group and groups of patients with psychogenic and organic nonarterial ED. The sensitivity and specificity of a PICAD value of 50% in diagnosis of arteriogenic ED were 100% and 98.2%, respectively. In all groups and in the entire sample of patients studied we did not find a correlation between PICAD and postocclusive changes in the diameter of brachial arteries. CONCLUSION: The method of ultrasound assessment of postocclusive changes in the diameter of cavernosal arteries is reliable and a highly informative tool for diagnosis of arteriogenic ED. It cannot be substituted by technically simpler method of ultrasound examination of brachial arteries, while results of the latter could help to define the necessity of performing an examination of cavernous arteries.

Adult↗

PubMed1999

Exhaled nitric oxide does not provide a marker of vascular endothelial function in healthy humans.

In the lung, nitric oxide synthase (NOS) has been found in both alveolar epithelial and vascular endothelial cells. Nitric oxide (NO) in the exhaled air stemming from the lower respiratory tract has been claimed to represent a marker of the vascular endothelial NO production. Experimental evidence for this concept, however, is lacking. We compared, in eight healthy volunteers, effects on exhaled NO of epithelial NOS inhibition by N (G)-monomethyl-L-arginine (L-NMMA) inhalation (6 mg/kg over 15 min) with those of endothelial NOS inhibition by L-NMMA infusion (25 microgram/kg/min for 30 min). We also measured blood pressure, heart rate, and L-NMMA plasma concentration. The major new findings were that L-NMMA inhalation which did not have any detectable effect on hemodynamics and L-NMMA plasma concentration, decreased the pulmonary exhaled NO by almost 40%. In contrast, L-NMMA infusion that inhibited endothelial NOS, as evidenced by an increase in blood pressure and a decrease in heart rate, had only a barely detectable effect on exhaled NO (-11 +/- 4% from baseline). Pulmonary exhaled NO is mostly of epithelial rather than endothelial origin, and does not provide a marker for vascular endothelial NO production and/or endothelial function in healthy humans.

Administration, Inhalation↗

PubMed2002

Placebo-controlled trial of transdermal estrogen therapy alone in postmenopausal women: effects on arterial compliance and endothelial function.

BACKGROUND: The cardiovascular effects of hormone replacement therapy (HRT) are controversial. Improvement in vascular function, potentially mediated, at least in part, via improvements in lipid profiles, is a proposed mechanism of estrogen action; however, there are few controlled human trials. We have studied the effects of HRT, independent of changes in lipid profile, with transdermal estrogen therapy, focusing on blood pressure, lipid profiles and vascular function, encompassing both biomechanical arterial properties (systemic arterial compliance and pulse wave velocity) and endothelial function (flow-mediated vasodilatation). METHODS: In this 2-year, double-blind, placebo-controlled, cross-over study, 34 healthy postmenopausal women were randomized to transdermal estrogen alone (Menorest, 50 micrograms) or placebo. After withdrawals, 25 women completed measurements at baseline, 6 weeks, 6 months and 12 months during both treatment phases. RESULTS: Transdermal estrogen did not improve blood pressure, lipid profiles or arterial function, compared with placebo. CONCLUSION: From this randomized, controlled trial, it appears that transdermal estrogen alone, in healthy postmenopausal women, does not improve lipid profiles or a spectrum of indices of arterial function, compared with placebo. These results would suggest that there might not be a beneficial effect of transdermal HRT on the vasculature in postmenopausal women.

Administration, Cutaneous↗

PubMed2006

Comparison of endothelial function, O2-* and H2O2 production, and vascular oxidative stress resistance between the longest-living rodent, the naked mole rat, and mice.

Vascular aging is characterized by decreased nitric oxide (NO) bioavailability, oxidative stress, and enhanced apoptotic cell death. We hypothesized that interspecies comparative assessment of vascular function among rodents with disparate longevity may offer insight into the mechanisms determining successful vascular aging. We focused on four rodents that show approximately an order of magnitude range in maximum longevity (ML). The naked mole rat (NMR; Heterocephalus glaber) is the longest-living rodent known (ML > 28 yr), Damara mole rats (DMRs, Cryptomys damarensis; ML approximately 16 yr) and guinea pigs (GPs, Cavia porcellus; ML approximately 6 yr) have intermediate longevity, whereas laboratory mice are short living (ML approximately 3.5 yr). We compared interspecies differences in endothelial function, O(2)(-)* and H(2)O(2) production, and resistance to apoptotic stimuli in blood vessels. Sensitivity to acetylcholine-induced, NO-mediated relaxation was smaller in carotid arteries from NMRs, GPs, and DMRs than in mouse vessels. Measurements of production of O(2)(-)* (lucigenin chemiluminescence and ethidium bromide fluorescence) and H(2)O(2) (dichlorofluorescein fluorescence) showed that free radical production in vascular endothelial and smooth muscle cells is comparable in vessels of the three longer-living species and in arteries of shorter-living mice. In mouse arteries, H(2)O(2) (from 10(-6) to 10(-3) mol/l) and heat exposure (42 degrees C for 15-45 min) enhanced apoptotic cell death, as indicated by an increased DNA fragmentation rate and increased caspase 3/7 activity. In NMR vessels, only the highest doses of H(2)O(2) enhanced apoptotic cell death, whereas heat exposure did not increase DNA fragmentation rate. Interspecies comparison showed there is a negative correlation between H(2)O(2)-induced apoptotic cell death and ML. Thus endothelial vasodilator function and vascular production of reactive oxygen species do not correlate with maximal lifespan, whereas increased lifespan potential is associated with an increased vascular resistance to proapoptotic stimuli.

Acetylcholine↗

PubMed1997

Measures of endothelial function as an endpoint in hypertension?

The vascular endothelial cell is a multipotent cell which has several functions: transport barrier, phagocytosis, coagulation/anticoagulation, fibrinolysis, autocrine/paracrine and metabolic functions. The release of vasoactive agents, such as the vasodilators EDRF (NO) and EDHF, and vasoconstrictors, such as endothelin (ET), represents an important local mechanism altering the balance of vasodilation/ vasoconstriction of the vascular smooth muscle cell. Inhibition of the synthesis of NO by exogenous (e.g. L-NAME) or endogenous (e.g. ADMA) L-arginine analogues may cause transient or sustained hypertension. A similar effect may be achieved by continuous administration of the potent vasoconstrictor ET. Endothelial dysfunction, associated with a deficient NO production and release as well an enhanced ET generation, may be present in some forms of vascular disease, such as hypertension, atherosclerosis, diabetes mellitus or sleep apnea. Whether such alterations may be a cause of hypertension and involved in the maintenance of high blood pressure or whether they represent a consequence of the hypertensive disease remains to be concluded. Furthermore, while there is emerging evidence that endothelial dysfunction in cardiovascular disease may be reversed by therapy, it remains to be determined whether measures of endothelial function in man may serve as predictors for morbidity or mortality.

Endothelium, Vascular↗

PubMed2005

Relation between peripheral vascular endothelial function and coronary flow reserve in patients with chest pain and normal coronary angiogram.

To evaluate the relation between peripheral vascular endothelial function and coronary flow reserve (CFR), we assessed flow mediated dilation (FMD) of brachial artery and the intima-media thickness (IMT) of the carotid artery in 32 subjects (mean age 58+/-9 years, M/F=9:23 ) with chest pain and normal coronary angiogram. The subjects were divided into 2 groups according to CFR >or=2.1 or <2.1 measured with transthoracic echocardiography in distal left anterior descending coronary artery. We found % FMD was decreased in the group with CFR <2.1 than those of CFR >or=2.1 and CFR was correlated with peripheral FMD. However, IMT was not different between two groups. These results suggest that microvascular dysfunction is primarily related to endothelial dysfunction rather than advanced atherosclerosis and because it is a generalized process that involves the whole arteries, the measurement of brachial FMD can be a useful diagnostic tool to evaluate microvascular dysfunction in patients with chest pain and normal coronary angiogram.

Aged↗

PubMed2000

Acute improvement of peripheral endothelial function in postmenopausal women with coronary artery disease after single oral intake of 17beta-estradiol valerate.

Chronic estrogen supplementation is known to improve endothelial function in postmenopausal women. We studied the acute effect of a single dose of orally administered 17beta-estradiol valerate (E2) on the peripheral endothelial dependent and independent vasodilatation in postmenopausal women with coronary artery disease (CAD). 20 postmenopausal women (age: 64.9 (7.2) y, height: 1.61 (0.04) m. weight: 68.6 (10.6) kg) with angiographically confirmed CAD were randomly examined for flow-associated vasodilatation (= FAD%, a marker for endothelial dependent vasodilatation) and for glyceryltrinitrate (400 microg, p.o.) induced vasodilatation (= GTN%, representing endothelial independent vasodilatation) two hours after placebo controlled, randomized crossover intake of 4 mg E2 p.o. After placebo FAD% was impaired (3.5 (1.7)%) compared to historic controls. After the oral intake of 4 mg E2, FAD% improved to 5.0 (2.8)% (P=0.02). GTN% was not significantly influenced by the oral E2 (E2: 12.6 (5.7) v placebo: 11.2 (6.9)%, P=0.14). Endothelial dysfunction can partially be restored by a single oral dose of 4 mg E2. This indicates an acute vasoprotective effect of E2 beyond its genomic and lipid modifying actions. It remains to be investigated if estrogen might play a beneficial role in the acute treatment of symptomatic coronary artery disease such as angina pectoris or preinfarct syndrome.

Aged↗

PubMed2006

Bosentan preserves endothelial function in mice overexpressing APP.

This study was designed to test the hypothesis that Alzheimer's disease (AD) is associated with endothelial dysfunction and that chronic endothelin-1 antagonism preserves endothelial function in mice overexpressing the AD amyloid precursor protein (APP). Three groups of mice were studied: C57BL/6 (normal control, n = 6), transgenic mice overexpressing APP (Tg2576, n = 5), and Tg2576 mice fed Bosentan (100 mg/(kg day)(-1)), a combined endothelin A and B receptor antagonist, for 4 months (Tg2576+Bosentan, n = 5). Mice were sacrificed at the age of 7 months. In vitro, the endothelium-dependent aortic vasorelaxation was significantly attenuated in Tg2576 mice as compared to C57BL/6 and Tg2576+Bosentan mice. In contrast, Tg2576+Bosentan and C57BL/6 mice showed similar endothelium-dependent aortic vasorelaxation. Similarly, endothelium-dependent carotid vasorelaxation was significantly attenuated in Tg2576 mice compared to C57BL/6 and Tg2576+Bosentan mice. There was no difference between the three groups in the response to nitroprusside. The current study demonstrates the presence of endothelial dysfunction in both carotid and aortic arteries in mice overexpressing APP and suggests a pathophysiological role for the endogenous endothelin system in AD.

Alzheimer Disease↗

PubMed1993

Effects of pressure and duration of hyperkalemic infusions on endothelial function.

Infusions of crystalloid hyperkalemic cardioplegic solutions (CHCSs) are known to impair endothelium-dependent coronary relaxation. This impairment might also be influenced by high perfusion pressure and duration of CHCS infusion. To verify this hypothesis, we designed experiments to study the influence of pressure and duration of CHCS infusion as modulating factors in CHCS-related endothelial impairment. Isolated hearts of Sprague-Dawley rats were studied in a Langendorff apparatus for coronary endothelial function. Hearts (n = 6) were exposed to four different CHCSs containing 12, 24, 40, or 100 mmol/L of potassium chloride (KCl). Endothelial and smooth muscle functions were respectively tested by infusion of 5-hydroxytryptamine (1 x 10(-6) mol/L) and sodium nitroprusside (1 x 10(-5) mol/L) before and after CHCS perfusion. In group I (n = 24), 37 degrees C CHCSs were perfused at 80 cm H2O of pressure for 30 minutes. In group II (n = 24), the same CHCSs were perfused at 160 cm H2O for 30 minutes. In group III (n = 18), CHCSs containing 24, 40, and 100 mmol/L of KCl were infused at 160 cm H2O for 10 minutes. In all groups, response to sodium nitroprusside was unaltered by CHCS infusion, indicating that smooth muscle function was preserved. However, in group II, 5-hydroxytryptamine-induced vasodilation was significantly impaired in hearts perfused with CHCS containing 24 mmol/L of KCl or more, suggesting endothelial damage. This study demonstrates that, in addition to KCl concentration, pressure and duration of infusion are two major determinants in CHCS-mediated endothelial damage.

Animals↗

PubMed1997

Preserved endothelial function in patients with severe hypertriglyceridemia and low functional lipoprotein lipase activity.

OBJECTIVES: We sought to determine whether hypertriglyceridemia in patients with lipoprotein lipase (LPL) dysfunction is associated with endothelial dysfunction in resistance vessels of the forearm vasculature. BACKGROUND: Vasodilator responses to acetylcholine, acting through stimulation of nitric oxide (NO) release from the endothelium, are impaired in hypercholesterolemia and normalized by L-arginine, suggesting dysfunction of the L-arginine/NO pathway. Similar abnormalities have been reported in conditions associated with hypertriglyceridemia, such as non-insulin-dependent diabetes. The relation between endothelial function and plasma triglyceride concentrations has, however, not previously been studied in vivo. METHODS: We examined forearm blood flow responses to brachial artery infusions of acetylcholine (alone and with L-arginine) and nitroprusside (an NO donor) in 17 patients with severe hypertriglyceridemia (mean [+/- SD] plasma triglyceride concentration 1,914 +/- 1,288 mg/dl) but normal low density lipoprotein cholesterol (89 +/- 31 mg/dl) and in 34 normolipidemic control subjects. Severe LPL dysfunction was demonstrated in 10 of 17 patients. RESULTS: Acetylcholine (7.5 and 15 microg/min) produced similar forearm blood flow responses in hypertriglyceridemic patients (mean [+/- SEM] 7.7 +/- 0.9 and 10.5 +/- 1.2 ml/min per 100 ml) and in control subjects (7.5 +/- 0.6 and 11.0 +/- 0.8 ml/min per 100 ml, p = 0.78 by analysis of variance). Responses to acetylcholine co-infused with L-arginine (10 mg/min) and nitroprusside (3 and 10 microg/min) were also similar in hypertriglyceridemic patients and control subjects (p = 0.93 and p = 0.27 for acetylcholine with L-arginine and nitroprusside, respectively). The ratio response to acetylcholine/response to nitroprusside differed between hypertriglyceridemic patients and control subjects by only 1%. The study had >90% power (alpha = 0.05) to detect a difference >30% in this ratio. CONCLUSIONS: Severe hypertriglyceridemia associated with LPL dysfunction is not associated with the degree of endothelial dysfunction seen in moderate hypercholesterolemia when responses to acetylcholine are impaired by >40%.

Acetylcholine↗

PubMedDate not supplied

Influence of type II diabetes on arterial tone and endothelial function in murine mesenteric resistance arteries.

An arteriograph was used to assess myogenic tone, smooth muscle contractility and the influence of endothelial function on mesenteric resistance artery reactivity in insulin-resistant mice (C57BL/KsJ-db/db) and age- and gender-matched wild-type mice. Increases in transmural pressure induced myogenic tone in arteries from both control and db/db mice. At 12 and 16 weeks of age, greater tone developed in diabetic than in control mice. In control, but not in db/db mice, pretreatment of arteries with L-NAME potentiated myogenic tone. Indomethacin and SQ29548 (PGH2/TXA2 receptor antagonist) had no efffect in control, but inhibited myogenic tone in db/db mice. Endothelium-dependent vasodilation induced by acetylcholine and bradykinin, was depressed in db/db mice and potentiated by SQ29548 and LY333531 (protein kinase C(beta) inhibitor). Messenger RNA expression levels for PKC(beta) were over-expressed 2.5-fold in db/db relative to those in control mice. However, expression levels of mRNA for eNOS, PKC(alpha), and PKC(xi) were similar in the db/db and control mice. Collectively, these results suggest that the greater myogenic tone in resistance arteries from diabetic mice may be attributable, to greater amounts of one or more vasoconstricting prostanoids. Our data indicate that in diabetic mice, basal and agonist-stimulated NO releases are depressed and NO-mediated vasorelaxation in these mice may be countered by an endogenous vasoconstrictive prostanoid. This prostanoid-induced vasoconstriction is mediated by a PKC(beta)-dependent mechanism. Therefore, heightened activation of PKC(beta) and release of a vasoconstrictor prostanoid could play a role in endothelial dysfunction associated with type II diabetes.

Acetylcholine↗