SEARCH · PubMed Health

Results for “Endothelial function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources

PubMed2000

Oral treatment with an antioxidant (raxofelast) reduces oxidative stress and improves endothelial function in men with type II diabetes.

AIMS/HYPOTHESIS: To determine whether raxofelast, a new water soluble antioxidant decreases oxidative stress and improves endothelial function in men with Type II (non-insulin dependent) diabetes mellitus. METHODS: We treated ten normotensive, normocholesterolaemic men with Type II diabetes and as controls ten healthy men matched with them for age with raxofelast (600 mg twice daily) for 1 week. Plasma 8-epi-PGF(2a), a non-enzymic oxidation product of arachidonic acid was measured by gas chromatography/mass spectrometry as an index of oxidative stress. Forearm vasodilator responses to brachial artery infusion of acetylcholine (7.5, 15 and 30 microg min(-1)) and of the nitric oxide donor nitroprusside (1, 3 and 10 microg min(-1)) were measured by strain gauge plethysmography. RESULTS: Plasma concentrations of 8-epi-PGF(2a), were greater in diabetic than in control men (0.99 +/- 0.20 vs 0.18 +/- 0.01 nmol 1(-1), means +/- SEM, p < 0.001) and fell after raxofelast (from 0.99 +/- 0.20 to 0.47 +/- 0.07 nmol 1(-1), p < 0.05) in diabetic men but not in control men. Blood flow responses to acetylcholine were lower (p < 0.05) in diabetic than in control men (7.4 +/- 1.0 vs 12.9 +/- 2.3 ml min(-1) x 100 ml(-1) for the highest dose). In diabetic men, but not in control men, raxofelast increased (p < 0.05) blood flow responses to acetylcholine (from 7.4 +/- 1.0 m x min(-1) x 100 ml(-1) to 11.3 +/- 2.3 ml x min(-1) x 100 ml(-1) at highest dose). Blood flow responses to nitroprusside were similar in control and diabetic men and in both groups were similar before and after raxofelast. CONCLUSION/INTERPRETATION: Oral treatment with raxofelast for 1 week reduces oxidative stress and improves endothelial function in men with Type II diabetes.

Acetylcholine↗

PubMed2000

Differential effects of oral and transdermal estrogen replacement therapy on endothelial function in postmenopausal women.

BACKGROUND: We determined whether the vascular effects of estradiol depend on the route of administration by comparing the effects of oral estradiol and transdermal placebo, transdermal estradiol and oral placebo, and transdermal placebo and oral placebo on in vivo endothelial function in 27 postmenopausal women. METHODS AND RESULTS: Endothelial function was assessed from blood flow responses to intrabrachial artery infusions of endothelium-dependent (7.5 and 15 microgram/min acetylcholine) and endothelium-independent (3 and 10 microgram/min of sodium nitroprusside) vasodilators at 0, 2, and 12 weeks. In the oral estradiol group, the increase in flow above basal during infusion of the low dose of acetylcholine at 0, 2, and 12 weeks averaged 6.0+/-0.8, 6.9+/-0.8, and 11.3+/-1.2 (P<0.01 versus 0 and 2 weeks) mL. dL(-1). min(-1) at 0, 2, and 12 weeks. The percentage increases versus 0 weeks averaged 21+/-14% at 2 and 120+/-34% at 12 weeks. During the high-dose acetylcholine infusion, the increase in flow above basal averaged 8.6+/-1.3, 10.2+/-1.5, and 15.1+/-1.8 (P<0.05 versus 0 weeks) mL. dL(-1). min(-1), respectively. The percentage increases versus 0 weeks averaged 22+/-10% at 2 weeks and 119+/-46% at 12 weeks. In the oral estradiol group, endothelium-independent vasodilatation also improved significantly, but less markedly than endothelium-dependent responses. In the transdermal and placebo groups, all vascular responses remained unchanged. Oral but not transdermal estradiol also induced significant decreases in LDL cholesterol and Lp(a) concentrations and an increase in HDL cholesterol within 2 weeks. CONCLUSIONS: We conclude that oral but not transdermal estradiol induces potentially antiatherogenic changes in in vivo endothelium-dependent vasodilatation and lipid concentrations.

Administration, Cutaneous↗

PubMed2003

Cardiological syndrome X. Non-invasive assessment of endothelial function and arterial compliance.

BACKGROUND: Mechanisms responsible for cardiological syndrome X are complex and not well understood. It has been postulated that impaired endothelial function and abnormal reactivity of coronary vessels may play a role in the pathogenesis of this condition. AIM: To assess mechanical properties of peripheral arterial vessels and both endothelium-dependent and endothelium-independent vessel reactivity in patients with or without atherosclerotic lesions in coronary arteries. METHODS: The study group consisted of 100 patients with typical angina and positive exercise test who underwent coronary angiography. Based on angiographic results, the patients were divided into two groups: 50 patients with normal coronary angiograms and 50 age- and gender-matched patients with at least one significant coronary artery lesion (coronary artery disease (CAD) group). The control group consisted of 40 healthy volunteers without risk factors of atherosclerosis. The compliance of arterial vessels was assessed by automatic measurement of pulse wave velocity (PWV). Endothelial function was examined by ultrasonographic measurement of the diameter of brachial artery following passive hyperaemia (endothelium-dependent vessel distension) and following nitroglycerine (endothelium-independent mechanism). RESULTS: Among all three studied groups, the PWV values were the highest in patients with CAD. Patients with syndrome X had significantly higher PWV than in controls. A cut-off PWV value of 10.5 m/s distinguished patients with syndrome X from those with CAD. Endothelium-dependent arterial distensibility was significantly lower in patients with syndrome X than in controls; the lowest values were observed in patients with CAD. Among patients with syndrome X, the endothelium-dependent arterial vessel distensibility was the only parameter significantly influencing PWV results. CONCLUSIONS: PWV was significantly increased in patients with syndrome X which suggests a decreased arterial vessel compliance. These results and the impairment of endothelium-dependent relaxation suggest a similar pathomechanism of altered arterial reactivity in patients with syndrome X and in patients with CAD.

Adult↗

PubMed2006

Asymmetrical dimethylarginine (ADMA) and coronary endothelial function in patients with coronary artery disease and mild hypercholesterolemia.

OBJECTIVE: To investigate the association of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and coronary endothelial function. METHODS AND RESULTS: In 289 patients with coronary artery disease we assessed coronary endothelium-dependent and -independent vascular responses to intracoronary infusion of acetylcholine, adenosine, and nitroglycerin, respectively, and determined plasma ADMA and l-arginine concentrations by HPLC. After 6 months of treatment with either cerivastatin, nifedipine, cerivastatin+nifedipine, or placebo, coronary vascular function testing as well as ADMA and l-arginine determinations were repeated. We observed no correlation of plasma ADMA or l-arginine concentration and coronary response to acetylcholine, adenosine or nitroglycerin baseline, and no correlation of changes of ADMA or l-arginine plasma concentration with changes in coronary function (all r and rho<0.3, all p>0.05). CONCLUSION: At physiological plasma concentrations ADMA appears to have only little impact on coronary endothelial function.

Acetylcholine↗

PubMed2004

Lack of direct effect of moderate hyperleptinemia to improve endothelial function in lean rat aorta: role of calorie restriction.

Leptin stimulates vascular sympathetic activity and NO release. The resulting effect of hyperleptinemia on endothelial function is unknown. Reduction of food intake associated with hyperleptinemia may mediate some of the vascular effects of leptin. This study was designed to assess the relative effects of short-term moderate caloric restriction and hyperleptinemia on vascular function in lean rat. Endothelium-dependent and -independent vasorelaxation, nitric oxide synthase (eNOS) expression and nitrite production were measured in lean rats receiving leptin subcutaneous infusion (-26% caloric intake, -4% body weight versus control) or moderate caloric restriction (pair-feeding) for one week. Plasma leptin was increased (P < = 0.05) by approximately 300% in the leptin-infused group, while it decreased (P < or = 0.05) by approximately 40% in calorie-restricted animals. Both leptin infusion and calorie restriction resulted in improved (P < 0.05) endothelium-dependent vasorelaxation to acetylcholine (EC50: -6.1 +/- 0.2 and -6.2 +/- 0.2 versus -5.4 +/- 0.2 in control) and unaltered endothelium-independent vasodilation to DEA-NONOate. Furthermore, in aortas from leptin-infused and calorie-restricted rats, expression of eNOS and nitrite production were increased (P < = 0.05) to similar extent compared to control animals. These findings suggest that moderate short-term calorie restriction with adaptive hypoleptinemia has independent beneficial effects on endothelial function in lean animals by enhancing eNOS expression and function. In addition, physiological hyperleptinemia does not independently contribute to improved vascular function above and beyond the effect of calorie restriction.

Animals↗

PubMed2002

Severity of hypertension affects improved resistance artery endothelial function by angiotensin-converting enzyme inhibition.

The purpose of this study was to determine whether there are differences in the restoration of endothelial function by angiotensin-converting enzyme inhibition based on the severity of hypertension. Forearm blood flow (FBF) was measured in 69 patients with essential hypertension (mild, n = 23; moderate, n = 29; and severe, n = 17 randomly assigned to treatment with either imidapril or amlodipine for 24 weeks in a double-blind fashion during reactive hyperemia and after sublingual administration of nitroglycerin. Imidapril augmented the FBF response to reactive hyperemia after 24 weeks of treatment in the mild and moderate hypertensive groups, but not in the severe hypertensive group. The augmentation of the FBF response to reactive hyperemia induced by imidapril was significantly greater in the moderate hypertensive group than in the mild hypertensive group. Amlodipine did not alter the FBF response to reactive hyperemia. The increase in FBF after the sublingually administered nitroglycerin was similar in all groups. The infusion of NG-monomethyl-l-arginine, a nitric oxide synthase inhibitor, abolished the enhancement of reactive hyperemia in the mild and moderate hypertensive groups treated with imidapril. These findings suggest that the effects of imidapril on endothelial function are affected by the severity of hypertension and that angiotensin-converting enzyme inhibitor-induced augmentation of reactive hyperemia may be due to increased nitric oxide production.

Adult↗

PubMed2007

Effect of oral glucose loading on endothelial function in normal-weight and overweight children.

The aim of the present study was to investigate the impact of acute hyperglycaemia on endothelial function in both normal-weight and overweight children. A total of 16 overweight [BMI (body mass index) > or =85th percentile] and 15 normal-weight (BMI <85th percentile) children were evaluated for FMD (flow-mediated dilation) at baseline and 30, 60 and 120 min after glucose ingestion. At 15 min following the measurement of the final FMD, 0.3 mg of sublingual nitroglycerine was administered and the brachial artery was imaged in order to assess endothelium-independent dilation. By design, the overweight children were significantly heavier (63.2+/-4.6 compared with 41.3+/-2.5 kg; P=0.0003) and had a greater percentage body fat (43.9+/-1.8 compared with 23.8+/-2.05%; P<0.0001) than the normal-weight children. The area under the curve in response to glucose administration was significantly (P<0.0001) greater in the overweight group for both glucose and insulin. The FMD area under the curve was not significantly different at baseline or between time points after glucose ingestion, nor was there a difference in response between the two groups. Endothelium-independent dilation in the normal-weight group was significantly greater compared with the overweight group (26.7+/-1.6 compared with 20.2+/-2.0% respectively; P=0.019). In conclusion, these results suggest that acute elevation of glucose and insulin in overweight and normal-weight children are not associated with impairment in endothelial function.

Blood Glucose↗

PubMed2005

Short-term angiotensin(1-7) receptor MAS stimulation improves endothelial function in normotensive rats.

In this study we evaluated the effect of angiotensin(1-7) and its nonpeptide analog, AVE 0991, on the endothelial function in vivo. The experiments were performed in conscious adult male Wistar rats, with polyethylene catheters implanted into the descending aorta (through left carotid artery), for injection of acetylcholine or sodium nitroprusside, femoral artery for mean arterial pressure and heart rate measurement; and femoral vein for drug administration. Increasing doses of acetylcholine (3.1 ng to 25.0 ng) or nitroprusside (1.0 microg to 10.0 microg) were administered before and 30 minutes after the start of the infusion of: angiotensin(1-7) (0.7 and 7.0 pmol/min); A-779 (180 pmol/min); angiotensin(1-7) (7.0 pmol/min) combined with A-779 (180 pmol/min); AVE 0991 (11, 45, and 230 pmol/min); AVE 0991 (45 pmol/min) combined with A-779 (180 pmol/min), or vehicle (6 microL/min). Baseline mean arterial pressure and heart rate were not altered during angiotensin(1-7) or AVE 0991 infusion. Angiotensin(1-7) (0.7 pmol/min) infusion produced a significant potentiation of the hypotensive effect of acetylcholine (3.1 ng: -9+/-1 mm Hg before; -18+/-2 mm Hg after; P<0.05). A similar potentiation was observed with the higher dose of angiotensin(1-7). As observed for angiotensin(1-7), infusion of AVE 0991 at 230 pmol/min potentiated the acetylcholine effect (3.1 ng: -8+/-2 mm Hg before; -16+/-2 mm Hg after; P<0.05). The potentiating effect was not observed for nitroprusside. A-779 or l-NAME treatment blocked the potentiation produced by angiotensin(1-7) or AVE 0991. Our data indicate that short-term stimulation of angiotensin(1-7) receptors improve endothelial function through facilitation of nitric oxide release.

Acetylcholine↗

PubMed2005

Alteration in endothelial function and modulation by treatment with pioglitazone in rabbit renal artery from short-term hypercholesterolemia.

The present study was undertaken to investigate endothelial function and epoxyeicosatrienoic acids (EETs), which is a cytochrome P-450 monooxygenase (CYP) metabolite and one of the candidates as an endothelium-derived hyperpolarizing factor (EDHF) in the renal artery isolated from short-term hypercholesterolemic rabbits, and also to characterize the effects of pioglitazone on it. Rabbits were fed normal, 0.5% cholesterol chow, or 0.5% cholesterol chow plus 300 ppm pioglitazone for 5 weeks. The tension of isolated renal artery rings was measured isometrically. Serum lipid levels were measured and morphometric analysis was performed. EET contents in the renal artery were also determined. The cholesterol chow diet for 5 weeks increased serum lipid levels, and pioglitazone had no influence on it. In the phenylephrine precontracted renal artery, the cholesterol chow did not affect acetylcholine-induced relaxation. The N(G)-nitro-l-arginine- and indomethacin-resistant endothelium-dependent relaxation induced by acetylcholine was significantly enhanced in rabbits receiving the cholesterol chow as compared to rabbits receiving the control diet, and pioglitazone normalized it. The resistant part of acetylcholine-induced relaxation was significantly inhibited when the renal artery was treated with charybdotoxin, an inhibitor of large- and intermediate-conductance Ca(2+)-activated K(+) channels, or N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a nonselective CYP inhibitor, and it was significantly inhibited by sulfaphenazole, a selective CYP2C9 inhibitor in rabbits receiving only the cholesterol chow. In KCl-precontracted renal artery, the cholesterol chow inhibited acetylcholine-induced relaxation and pioglitazone normalized it. The cholesterol chow increased the production of EETs and reduced nitrate/nitrite contents in the renal artery, and pioglitazone strongly suppressed them. These results suggest that the EETs may be one of the EDHFs in the rabbit renal artery and beneficial effects of pioglitazone on alterations in endothelial function induced by cholesterol feeding are due, in part, to the protective action on the nitric oxide system and/or the suppression of increased production of EETs.

Acetylcholine↗

PubMed2006

The effect of vardenafil on endothelial function of brachial and cavernous arteries.

The aim of the present study was to examine the effect of new phosphodiesterase type 5 inhibitor vardenafil on endothelial function of cavernous and brachial arteries in healthy men and in patients with different forms of erectile dysfunction (ED). This prospective, double-blind, placebo-controlled study was performed on 135 men with ED and 30 healthy controls. Complex evaluation was performed in all patients with ED. All participants also underwent our modification of ultrasound (US) assessment of postocclusive changes in the diameter of cavernosal arteries and endothelium-dependent flow-mediated dilation (FMD) of the brachial artery before and 1 h after administration of 20 mg of vardenafil or placebo. After study drug administration, PICAD and FMD significantly increased in patients receiving vardenafil (P < 0.001) but not in patients receiving placebo. Increase in PICAD values was significantly greater in patients with arteriogenic ED compared with patients with organic nonarterial ED (P = 0.007), psychogenic ED (P < 0.001) and controls (P = 0.001). The most prominent increase in brachial artery FMD values were found in patients with arteriogenic ED, although statistically significant differences were present only between patients with arteriogenic ED and control group (P = 0.035). We have found a moderate negative correlation between initial PICAD and its increase after vardenafil and between pretreatment flow-mediated vasodilation of brachial arteries and its increase after vardenafil administration (r = -0.57 and -0.55, respectively). These findings suggest that the use of vardenafil restores impaired endothelial function of cavernous and brachial arteries.

Adult↗

PubMedDate not supplied

Bradykinin as a major endogenous regulator of endothelial function.

Healthy vascular endothelium is a powerful generator of nitric oxide (NO), prostacyclin (PGI2), prostaglandin E2 (PGE2), and plasminogen activator (t-PA). These endothelial products protect vascular wall against aggression from activated blood platelets and leukocytes. In particular they protect against thrombosis, promote thrombolysis, maintain tissue perfusion, and inhibit remodeling of vascular and cardiac walls. Endothelial dysfunction appears on one hand as suppression in the release of the above mediators, and on the other as deleterious discharge of prostaglandin endoperoxides (PGH2, PGG2), superoxide anion O2-, peroxynitrite (ONOO-), and plasminogen activator inhibitor (PAI-1). Our data point to endothelial bradykinin (Bk) as a trigger for protective endothelial mechanisms. In cultured endothelial cells (CEC) Bk through kinin B2 receptors raised in a concentration-dependent manner (1pM-10 nM) free cytoplasmic calcium ions [Ca2+]i. This rise was accompanied by the release of NO as quantified by a porphyrinic sensor. Other endothelial agonists were weaker-stimulators of [Ca2+]i than Bk. In vivo we analyed the effects of exogenous Bk and of amplifiers of endogenous Bk, such as perindopril and quinapril ("tissue type" angiotensin converting enzyme inhibitors, ACE-I) on endothelial function using our original thrombolytic bioassay and EIA assays for 6-keto-PGF1alpha and t-PA antigen. A major difference found between exogenuous Bk and endogenous Bk (that rendered by "tissue ACE-I") was a) prolonged thrombolytic action (> 4h) of quinapril or perindopril. Moreover, only exogenous Bk evoked an immediate and profound hypotensive action. In vivo, Bk-induced thrombolysis was B2 kinin receptor-dependent, PGI2-mediated. The unexpected action of Bk came to light in CEC. Then appeared incubated for 4 h increased expression of mRNAs for haemoxygenase (HO-1), cyclooxygenase 2 (COX-2), prostaglandin E synthase (PGE-S), but hardly for nitric oxide synthase 2(NOS-2). We hypothesize that a network of interactions of Bk-induced enzymes may constitute a delayed phase of Bk effects in the endothelium, whereas the primary phase would be activation by BK of [Ca2+]i-dependent constitutive endothelial enzymes. In blood-perfused rat endotoxemic lungs, NO is the most eminent cytoprotective mediator. Summing up, in peripheral circulation endogenous Bk is the most efficient activator of protective endothelial function. Thrombolytic action of "tissue-type" ACE-Is relies on receptor B-2-mediated, [Ca2+]i-dependent release of PGI2. Bk also may act as a "microcytokine" by inducing mRNAs for HO-1, COX-2, or PGE-S. Activation of HO-1 may lead to a deficiency in intracellular heme required as a cofactor for both COX and NOS. This network of interactions triggered by Bk call for further studies.

Animals↗

PubMed2006

Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction.

We evaluated the effect of a chronic treatment with Tadalafil on progenitor cells (PCs) number and endothelial function in patients with erectile dysfunction (ED) with or without cardiovascular risk factors. Twenty-six subjects with ED and 23 aged matched controls were studied. All subjects underwent blood tests, International Index of Erectile Function (IIEF-5), Nocturnal Penile Tumescence Rigidity Monitoring test (NPTRM), brachial artery flow-mediated dilation (FMD) and PCs count. International index of erectile function, FMD and PC count were re-evaluated in all subjects at the end of Tadalafil and placebo treatment. With respect to controls patients had lower basal FMD (P < 0.05) and basal PCs (P < 0.05). Treatment with Tadalafil determined a significant increase in PCs (P < 0.001) and FMD (P < 0.001) with respect to basal level. Positive correlation was found between basal FMD and PCs (P < 0.05) and between basal FMD and PCs increase after Tadalafil treatment (P < 0.05). Tadalafil promotes a mobilization of PCs and improves endothelial function in ED patients.

Adult↗

PubMed2005

Tyrosine phosphorylation and the small GTPase rac cross-talk in regulation of endothelial barrier function.

Endothelial barrier function depends on the integrity of intercellular adherens junctions controlled by the association of VE-cadherin/catenin complex with cortical actin filaments. Both tyrosine phosphorylation/dephosphorylation of junctional proteins and actin reorganization mediated by rho-GTPases regulate barrier function but the relationship between these regulatory mechanisms is unclear. Here we studied the effects of factors increasing protein tyrosine phosphorylation, pervanadate (PV) and VEGF, on distribution of VE-cadherin, F-actin polymerization and transendothelial electrical resistance (TER) in human umbilical vein endothelial cells (HUVECs). Changes in protein tyrosine phosphorylation of cytoplasmic and junctional proteins, as well as the activity of rho-GTPase racl, were also measured. We report for the first time that PV and VEGF induced a rapid transient increase in endothelial barrier function accompanied by rac1 activation, a differentiated tyrosine phosphorylation of the VE-cadherin/catenin complex, recruitment of actin filament to cell junctions and ruffle formation. A sustained decrease in endothelial barrier function was observed at later times of PV and VEGF treatment. Expression of dominant negative rac1, N17rac1 abolished the barrier-enhancing effects of PV and VEGF, while the sustained decrease in barrier function was unaffected. These observations bring into focus early short-term effects of protein tyrosine phosphorylation in cells, often overshadowed by more pronounced and long-lasting later effects and may play an important role in the regulation of endothelial barrier function.

Actins↗

PubMed2004

Impaired endothelial function of the retinal vasculature in hypertensive patients.

BACKGROUND AND PURPOSE: Arterial hypertension constitutes a central factor in the pathogenesis of stroke. We examined endothelial function of the retinal vasculature as a model of the cerebral circulation. METHODS: Thirty-eight young subjects (19 hypertensive and 19 normotensive) were treated with the AT1-receptor blocker candesartan cilexetil and placebo, each over 7 days. Retinal capillary flow and blood flow velocity in the central retinal artery were assessed with scanning laser Doppler flowmetry and pulsed Doppler ultrasound, respectively. N(G)-monomethyl-L-arginine (L-NMMA) was infused to inhibit nitric oxide (NO) synthesis. Diffuse luminance flicker was applied to stimulate NO release. RESULTS: In normotensive subjects, L-NMMA decreased retinal capillary flow by 8.2%+/-13% (P<0.05) and flickering light increased mean blood flow velocity in the central retinal artery by 19%+/-29% (P<0.01). In contrast, no significant change to these provocative tests was seen in hypertensive subjects. Treatment with candesartan cilexetil restored a normal pattern of reactivity in retinal capillaries (l-NMMA: decrease in perfusion by 10%+/-17%, P<0.05) and the central retinal artery (flicker: increase in mean blood flow velocity by 42%+/-31%, P<0.001) in hypertensive patients. CONCLUSIONS: Endothelial function of the retinal vasculature is impaired in early essential hypertension but can be improved by AT1-receptor blockade.

Adult↗

PubMed2001

Acute effects of vitamin C on platelet responsiveness to nitric oxide donors and endothelial function in patients with chronic heart failure.

Chronic heart failure (CHF) is characterized by a prothrombotic state, which may relate to increased platelet aggregability, endothelial dysfunction, and increased oxidative stress. We investigated the effect of vitamin C in CHF on ex vivo platelet aggregation and platelet responsiveness to the anti-aggregatory effects of the nitric oxide (NO) donors glyceryl trinitrate (GTN) and sodium nitroprusside (SNP). We also examined parameters of oxidative stress and endothelial function in patients. In this double-blind, randomized, crossover study vitamin C (2 g) or placebo was given intravenously to 10 patients with CHF. We measured adenosine 5-diphosphate (ADP)-induced platelet aggregation, flow-mediated dilatation (FMD) in the brachial artery using ultrasonic wall-tracking, and plasma levels of lipid-derived free radicals using electron paramagnetic resonance spectroscopy. Vitamin C did not affect ex vivo platelet aggregability but enhanced the inhibition of platelet aggregation by SNP (62.7+/-10.2 to 82.7+/-4.8%, p = 0.03) and tended to increase responses to GTN (40.5+/-9.0 to 53.4+/-7.3, p = 0.06). The effect of vitamin C on platelet responsiveness to the antiaggregatory effects of SNP was inversely related to basal response to SNP (r = -0.9, p < 0.01); a similar trend was observed with GTN (r = -0.6, p = 0.1). Vitamin C also increased FMD (1.9+/-0.6 to 5.8+/-1.5%, p = 0.02) and reduced plasma lipid-derived free radicals by 49+/-19% (p < 0.05). In patients with CHF acute intravenous administration of vitamin C enhances platelet responsiveness to the anti-aggregatory effects of NO donors and improves endothelial function, suggesting a potential role for vitamin C as a therapeutic agent in CHF.

Adult↗

PubMed1997

Improved endothelial function with angiotensin-converting enzyme inhibitors.

Associations between coronary events and plasma renin activity, and between coronary risk reduction and angiotensin-converting enzyme (ACE) inhibitors, are now well recognized. Improvement in endothelial function may explain, in part, some of the effects of ACE inhibitors in reducing the rates of adverse cardiovascular outcomes observed in clinical trials. ACE inhibitors have been shown to restore the endothelium-mediated vascular relaxation response in animal models of severe atherosclerosis. Clinical trials are now under way to examine the effect of ACE inhibitors on surrogate outcomes that allow assessment of endothelial function in the progression of carotid and coronary atherosclerosis. The recently completed Trial on Reversing ENdothelial Dysfunction (TREND) demonstrated improved coronary endothelium-dependent vasomotor function after 6 months of treatment with quinapril. In addition, quinapril treatment was associated with a trend toward an increase in microvascular blood flow response. Other studies in progress will assess the effect of ACE inhibitors on clinical coronary risk and plaque progression.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Mechanisms of the protective effects of urocortin on coronary endothelial function during ischemia-reperfusion in rat isolated hearts.

1 Urocortin is a vasodilator peptide related to corticotrophin-releasing factor, which may protect endothelial function during coronary ischemia-reperfusion (I-R). The aim of this study was to study the mechanisms of this protective effect. 2 Hearts from Sprague-Dawley rats were isolated and perfused at constant flow and then exposed to 15 min global zero-flow ischemia, followed by 15 min reperfusion. The relaxation to acetylcholine (10 nM-10 microM) was recorded after pre-constriction of the coronary vasculature with U46619 (100-300 nM) in ischemic-reperfused or time-control hearts. 3 After I-R, the coronary relaxation to acetylcholine was reduced and this reduction was attenuated by treatment with urocortin (10 pM), administered before ischemia and during reperfusion. 4 This urocortin-induced improvement of the relaxation to acetylcholine was not modified by tetraethylammonium (10 mM), blocker of Ca2+ dependent-potassium channels; glibenclamide (10 microM), blocker of K(ATP) channels; N(w)-nitro-L-arginine methyl ester (L-NAME, 100 microM), blocker of nitric oxide synthesis; or meclofenamate (10 microM), blocker of cyclooxygenase, but it was abolished by chelerythrine (3 microM), blocker of protein kinase C (PKC). 5 These results suggest that urocortin may protect coronary endothelial function during I-R by activation of PKC.

Acetylcholine↗

PubMed2005

Endothelial function in patients with sickle cell anemia during and after sickle cell crises.

BACKGROUND: Prior studies have demonstrated increased adherence of sickle cell erythrocytes to vascular endothelial cells. While decreased production of nitric oxide and increased production of adhesion molecules have been implicated in this pathophysiology, the relative contribution of these mechanisms during acute sickle cell crises as compared to steady state conditions have not been elucidated. METHODS AND RESULTS: We studied 10 consecutive young adult patients presenting with a sickle cell crisis. Endothelial function was evaluated by a non-invasive brachial artery shear stress method. Serum levels of adhesion molecules were obtained during the crisis. Both brachial artery responsiveness and serum levels of adhesion molecules were then repeated at steady state. Ten age and gender matched volunteers served as a control group. Impaired endothelial function and impaired endothelium-independent vasodilatation were observed in all sickle cell patients during both steady state and during crisis. Flow mediated dilation (FMD)% was 3.25+/- 2.76% during crisis, 4.57+/- 4.11 at steady state, compared with the control group FMD of 11.64+/- 7.69% (p< 0.001). Flow independent dilation was 10.35+/- 11.3% during crisis, 10.03+/- 6.52% at steady state, compared with control group FID of 24.17+/- 11.87% (p< 0.001). Levels of cell adhesion molecules and markers of inflammation were increased in sickle cell crisis patients compared with the control group: sCD40 ligand levels during the acute crisis were over twice the level of normal matched volunteers (p=0.02), and similarly significant increases were seen for E-selectin (p=0.008), ICAM-1 (p=0.037) and VCAM-1 levels (p=0.01). The levels of each of these biomarkers was not significantly increased during acute crises as compared to patients' recovery state. CONCLUSIONS: Sickle cell anemia patients have severe systemic endothelial dysfunction as demonstrated by both brachial artery assessment and increased serum levels of adhesion molecules. These abnormalities characterize not only the sickle cell crisis but also the steady state pathophysiology of sickle cell anemia.

Adolescent↗