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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction accompanies suboptimal glucose control in patients with diabetes mellitus. A hallmark of endothelial dysfunction is a deficiency in production or bioavailability of vascular nitric oxide (NO). Here we demonstrate that acute exposure of human endothelial cells to glucose, at levels found in plasma of diabetic patients, results in a significant blunting of NO responses to the endothelial nitric oxide synthase (eNOS) agonists bradykinin and A-23187. Monitoring of NO generation by purified recombinant bovine eNOS in vitro, using amperometric electrochemical detection and an NO-selective porphyrinic microelectrode, showed that glucose causes a progressive and concentration-dependent attenuation of detectable NO. Addition of glucose to pure NO solutions similarly elicited a sharp decrease in NO concentration, indicating that glucose promotes NO loss. Electrospray ionization-tandem mass spectrometry, using negative ion monitoring, directly demonstrated the occurrence of a covalent reaction involving unitary addition of NO (or a derived species) to glucose. Collectively, our findings reveal that hyperglycemia promotes the chemical inactivation of NO; this glucose-mediated NO loss may directly contribute to hypertension and endothelial dysfunction in diabetic patients.
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PMID:Glucose scavenging of nitric oxide. 1118 10

Vascular endothelium is involved in the regulation of vascular tone, vessel permeability, and angiogenesis. Vessel tone is determined by the balance of various paracrine vasodilatory and vasoconstrictor factors, most notably nitric oxide (NO) and endothelin-1. Not surprisingly, endothelial dysfunction is believed to be crucial in the development of the chronic vascular complications of diabetes. Endothelial dysfunction, which may be examined by studying endothelial-dependent vasodilatation in humans, is also disturbed by many of the individual features of the insulin resistance syndrome including hypertension, dyslipidaemia, and hyperglycaemia. Therefore, it may be possible that endothelial dysfunction could be closely associated with, or even a common antecedent of, the insulin resistance syndrome (IRS). There is emerging evidence that impaired endothelial-dependent vasodilatation is present in populations at future risk of diabetes and even in children of low birth weight, who may exhibit features of the insulin resistance syndrome in later life. Endothelial dysfunction is an obvious therapeutic target if the vascular pathology associated with insulin resistance and type 2 diabetes is to be ameliorated.
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PMID:The association between insulin resistance and endotheliopathy. 1122 Feb 84

Endothelial dysfunction is associated with hypertension, hypercholesterolemia, and heart failure. We tested the hypothesis that spontaneously diabetic Goto-Kakizaki (GK) rats, a model for type 2 diabetes, exhibit endothelial dysfunction. Rats also received a high-sodium diet (6% NaCl [wt/wt]) and chronic angiotensin type 1 (AT(1)) receptor blockade (10 mg/kg PO valsartan for 8 weeks). Compared with age-matched nondiabetic Wistar control rats, GK rats had higher blood glucose levels (9.3+/-0.5 versus 6.9+/-0.2 mmol/L for control rats), 2.7-fold higher serum insulin levels, and impaired glucose tolerance (all P<0.05). Telemetry-measured mean blood pressure was 15 mm Hg higher in GK rats (P<0.01) compared with control rats, whereas heart rates were not different. Heart weight- and kidney weight-to-body weight ratios were higher in GK rats (P<0.05), and 24-hour albuminuria was increased 50%. Endothelium-mediated relaxation of noradrenaline-precontracted mesenteric arterial rings by acetylcholine was impaired compared with the control condition (P<0.05), whereas the sodium nitroprusside-induced relaxation was similar. Preincubation of the arterial rings with the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester and the cyclooxygenase inhibitor diclofenac inhibited relaxations to acetylcholine almost completely in GK rats but not in Wistar rats, suggesting that endothelial dysfunction can be in part attributed to reduced relaxation via arterial K(+) channels. Perivascular monocyte/macrophage infiltration and intercellular adhesion molecule-1 overexpression were observed in GK rat kidneys. A high-sodium diet increased blood pressure by 24 mm Hg and 24-hour albuminuria by 350%, induced cardiac hypertrophy, impaired endothelium-dependent relaxation further, and aggravated inflammation (all P<0.05). The serum level of 8-isoprostaglandin F(2alpha), a vasoconstrictor and antinatriuretic arachidonic acid metabolite produced by oxidative stress, was increased 400% in GK rats on a high-sodium diet. Valsartan decreased blood pressure in rats fed a low-sodium diet and prevented the inflammatory response. In rats fed a high-sodium diet, valsartan did not decrease blood pressure or improve endothelial dysfunction but protected against albuminuria, inflammation, and oxidative stress. As measured by quantitative autoradiography, AT(1) receptor expression in the medulla was decreased in GK compared with Wistar rats, whereas cortical AT(1) receptor expression, medullary and cortical angiotensin type 2 (AT(2)) receptor expressions, and adrenal ACE and neutral endopeptidase expressions were unchanged. A high-sodium diet did not influence renal AT(1), AT(2), ACE, or neutral endopeptidase expressions. In valsartan-treated GK rats, the cortical and medullary AT(1) receptor expressions were decreased in the presence and absence of a high-sodium diet. A high-sodium diet increased plasma brain natriuretic peptide concentrations in presence and absence of valsartan treatment. We conclude that hypertension in GK rats is salt sensitive and associated with endothelial dysfunction and perivascular inflammation. AT(1) receptor blockade ameliorates inflammation during a low-sodium diet and partially protects against salt-induced vascular damage by blood pressure-independent mechanisms.
Hypertension 2001 Feb
PMID:Endothelial dysfunction and salt-sensitive hypertension in spontaneously diabetic Goto-Kakizaki rats. 1123 Mar 14

Endothelial dysfunction, believed to underlie the structural changes of atherosclerosis, is a systemic phenomenon. Despite this, the radial artery has been considered as devoid of atherosclerosis and is commonly used as a conduit in coronary artery bypass grafting (CABG). Recently, histological study has shown intimal hyperplasia and other structural changes consistent with early atherosclerosis in the radial artery. The objective of the present study was to determine if structural changes in the radial artery could be detected in vivo in patients with coronary atherosclerosis. Using high resolution echo-tracking, measurements of radial artery internal diameter, wall thickness and wall cross-sectional area were made in 25 patients awaiting CABG and in 20 controls. Digital and brachial blood pressures were also recorded. Mean arterial pressures did not differ between the patient and control groups. All measures of wall thickness were greater in the patient than the control group. Neither current arterial pressures nor past history of hypertension correlated with wall thickness. Using a model of analysis of covariance, coronary artery disease was the best single predictor of intima-media thickness, R(2)=48%, n=44, P<0.0005. We concluded that increased radial artery wall thickness can be demonstrated in vivo in patients with coronary atherosclerosis. This is a novel observation which seems to be independent of blood pressure, and is consistent both with the hypothesis of systemic endothelial dysfunction leading to systemic structural changes and also to the recent histological evidence for atherosclerotic changes in this vessel.
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PMID:Radial artery hypertrophy occurs in coronary atherosclerosis and is independent of blood pressure. 1129 91

Endothelial dysfunction associated with both menopause and hypertension could be one of the possible explanations for increased cardiovascular morbidity and mortality in hypertensive postmenopausal women. The aim of the present study was to investigate the long-term effect of menopause (bilateral ovariectomy) on endothelial function in isolated aortic rings of spontaneously hypertensive rats (SHR). Aortic rings were suspended in organ chambers filled with physiological salt solution (95% O2, 5% CO2, 37 degrees C), and isometric tension was measured. In studies designed to assess the tone-related release of nitric oxide (NO) from phenylephrine-precontracted aortic rings, we found that vasoconstriction induced by L-NAME was greater in aortic rings from sham-ovariectomized SHR (SHAM SHR) than in those obtained from ovariectomized SHR (OVX SHR). Concentration-related relaxant responses to superoxide dismutase were significantly greater in the SHAM SHR than in the OVX SHR. In contrast, receptor-mediated release of NO was not altered by ovariectomy, as deduced from acetylcholine (ACh) concentration-responses curves. Responses to the exogenous NO donor sodium nitroprusside (SNP) were also identical in both ovariectomized and sham-ovariectomized groups, ruling out differences in smooth muscle reactivity to NO. These results show that NO release is impaired in OVX SHR, an animal model of simultaneous hypertension and menopause.
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PMID:Long-term effect of bilateral ovariectomy on endothelial function in aortic rings of spontaneously hypertensive rats: role of nitric oxide. 1137 13

1. Endothelial dysfunction is seen in patients with essential hypertension or congestive heart failure (CHF). The present study aimed to evaluate the direct effect on endothelium- dependent vasodilation (EDV) of different pharmacological drugs commonly used in the treatment of these conditions. 2. Forearm blood flow (FBF) was measured in 37 young healthy normotensive subjects with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh; 2-4 microg/min), evaluating EDV, and sodium nitroprusside (SNP; 5-10 microg/min), evaluating endothelium-independent vasodilation (EIDV). The measurements of EDV and EIDV were undertaken under baseline conditions and were repeated after 1 h intra-arterial infusion of digoxin (0.1 mg/h), furosemide (5.0 mg/h), enalaprilat (2,4 mg/h), metoprolol (1.2 mg/h) or saline (controls). 3. Enalaprilat and digoxin improved the FBF response to MCh at 4 microg/min (from 22.7+/-2.3 to 25.5+/-2.1 mL/min per 100 mL tissue (P < 0.01) and from 18.2+/-2.4 to 22.2+/-2.0 mL/min per 100 mL tissue (P < 0.05), respectively). No significant changes where induced by furosemide or metoprolol in response to MCh at 4 microg/min (from 19.4+/-2.0 to 22.9+/-2.8 and from 15.3+/-2.4 to 14.7+/-1.1 mL/min per 100 mL tissue, respectively). No significant changes in basal FBF or EIDV were induced by the different drugs. When the endothelial function index was calculated as the MCh: SNP FBF ratio, a significant improvement was seen only with enalaprilat (1.1+/-0.1 to 1.2+/-0.1; P < 0.01) and furosemide (1.0+/-0.1 to 1.3+/-0.4; P < 0.05). 4. In conlusion, the results of the present study show that enalaprilat and furosemide improve endothelial vasodilatory function, while no major effect was induced by digoxin or metoprolol. Thus, different direct effects on the endothelium in young normotensive subjects were induced by drugs commonly used in the treatment of hypertension or CHF.
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PMID:Effects of digoxin, furosemide, enalaprilat and metoprolol on endothelial function in young normotensive subjects. 1138 May 10

Endothelial dysfunction is generally believed to be the inciting event in atherosclerosis, and is probably important in ischemic manifestations as well. The release of endothelium-derived vasoactive substances is not only triggered by acetylcholine, but also controlled by a host of neuromediators and by shear forces exerted by the blood flowing through the blood vessel. However, this balance is altered in disease states such as atherosclerosis, diabetes, chronic heart failure, coronary artery disease, or hypertension. The most important mechanism in the decrease in endothelium-dependent relaxation appears to be a reduced release of nitric oxide. In healthy people, the predominant effect of stimulation of the endothelium is vasodilation. It is tempting to hypothesize that endothelial dysfunction is one of the initial steps involved in the development of atherosclerosis, but also in peripheral artery atherosclerosis. Impairment of endothelium-dependent vasodilation in the coronary arteries has been demonstrated not only in patients with documented atherosclerosis and/or established cardiovascular risk factors. Noninvasive evaluation of brachial artery vasoactivity using high resolution B-mode ultrasound is currently being established to evaluate endothelial function. We studied the endothelial function in 50 normal volunteers, 28 hypertensive subjects, and 31 hypercholesterolemia subjects. The diameter of the target artery was measured from two-dimensional ultrasound images with 10 MHz linear transducer. The results suggested that antihypertensive therapy with a certain calcium antagonist did not have a favorable effect on endothelial function and after cessation of cholesterol lowering therapy, the endothelial dysfunction developed again. The endothelial function can now be readily measured in humans and is very useful research tool to assess the effect of risk factors and their treatment on vascular function. Endothelial function testing will assume a prominent role in the evaluation and treatment of patients at risk of developing coronary atherosclerosis and its sequelae.
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PMID:Noninvasive evaluation of endothelial function. 1143 34

Vascular structure, function, and mechanics are altered in hypertension, which contributes to an important degree to complications of elevated blood pressure. Vascular hypertrophy with collagen deposition and increased stiffness is found in large arteries, whereas in small arteries, smooth muscle cells are restructured around a smaller lumen, and there is no net growth of the vascular wall, particularly in milder forms of hypertension. Hypertrophic remodeling and increased small artery stiffness may be found in more severe hypertension. Endothelial dysfunction occurs in large or smaller vessels in a variable percentage of patients, particularly in presence of other risk factors such as diabetes, smoking, dyslipidemia, and advanced atherosclerosis. In clinical trials, 1-year treatment with angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and long-acting calcium channel blockers corrected small artery structure and endothelial dysfunction in hypertensive patients, whereas beta-adrenergic receptor blockers did not. Improved outcomes in hypertensive patients demonstrated in recent trials with some but not others of these agents could be a consequence, at least in part, of vascular protection offered by some antihypertensive agents.
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PMID:Small artery remodeling in hypertension: can it be corrected? 1146 50

Remodeling of large and small arteries in hypertension contributes to elevation of blood pressure, and may participate in the complications of hypertension. Large arteries exhibit increased lumen size, thickened media with increased collagen deposition, and decreased compliance, which contributes to raised systolic blood pressure and pulse pressure. In small (resistance) arteries smooth muscle cells are restructured around a smaller lumen, without true hypertrophy, particularly in milder forms of hypertension, whereas in severe forms and in secondary hypertension hypertrophic remodeling has been reported. Endothelial dysfunction occurs in many patients, with prevalence similar to that of left ventricular hypertrophy. Treatment with angiotensin-converting enzyme inhibitors, angiotensin receptor subtype 1 antagonists and long-acting calcium channel blockers has corrected changes in large and small arteries in hypertensive patients. Treatment with beta-blockers did not modify either structure or function of small arteries. Improved outcomes were reported in clinical trials with drugs that exert vascular protective effects, such as angiotensin-converting enzyme inhibitors and angiotensin receptor subtype 1 antagonists, as well as with those that do not appear to improve vascular structure or function. Recent trials suggest that these different drugs may provide similar benefits essentially through blood pressure lowering, although some minor differences between drugs have been noted. For example, the alpha-blocker doxasozin has been associated with worse outcomes (heart failure) than have diuretics. That hard end-point clinical trials have not demonstrated any advantages of agents with vasculoprotective properties may relate in part to the relatively short duration of some of these multicenter trials (3-5 years). Another contributing factor may be the low number of events with each drug class in the longer trials. Thus, current evidence does not support the rational expectation that vasculoprotective antihypertensive agents will be associated with better outcomes in hypertensive patients, possibly because of limitations of these trials.
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PMID:Effects of antihypertensive drugs on vascular remodeling: do they predict outcome in response to antihypertensive therapy? 1149 55

The focus of attention in preventing and treating cardiovascular (CV) disease today is shifting toward the arterial wall. Evidence has been accumulating for several years that protecting the endothelium is key to reducing CV risk. Endothelial dysfunction results in reduced compliance, or increased arterial stiffness, particularly in the smaller arteries. This abnormality is characteristic of patients with hypertension but may also be seen in normotensive patients before the appearance of clinical disease. Reduced arterial compliance is also seen in patients with diabetes and in smokers, and is part of a vicious cycle that further elevates blood pressure, aggravates atherosclerosis, and leads to increased CV risk. Although other factors are involved, the damage to the endothelium results in reduced secretion of nitric oxide, which influences smooth muscle growth, migration, and contraction, as well as influencing inflammation and clotting. Arterial compliance can be measured by several techniques, most of which are invasive or otherwise not clinically appropriate. Pulse contour analysis is a newly developed noninvasive method that allows for easy, in-office measurement of arterial elasticity to identify patients at risk for CV events before disease becomes clinically apparent. Further research is needed to confirm whether this method offers a means of improving risk stratification and therapeutic decision making.
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PMID:Arterial compliance to stratify cardiovascular risk: more precision in therapeutic decision making. 1149 6


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