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

Endothelial dysfunction has been found to be less severe in female than in male spontaneously hypertensive rats (SHR), which could contribute to the gender differences observed in the extent and rate of progression of hypertension in SHR. However, the influence of gender on the roles of different endothelium-derived mediators in the arterial responses in hypertension have not been evaluated in detail. Therefore, contractile and relaxation responses of mesenteric arterial rings in vitro were studied in female and male SHR, with normotensive female and male Wistar-Kyoto rats (WKY) serving as controls. In norepinephrine (NE)-precontracted arterial rings, endothelium-dependent relaxations to ACh as well as endothelium-independent dilations to sodium nitroprusside were more pronounced in female than in male SHR, whereas relaxations to the beta-adrenoceptor agonist isoproterenol remained equally impaired in female and male SHR. The cyclooxygenase inhibitor diclofenac, which reduces the synthesis of dilating and constricting prostanoids, markedly enhanced the relaxations to ACh in male SHR but not in the other groups. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester attenuated the relaxations to ACh more effectively in female SHR and WKY than in the male groups. However, when endothelium-dependent hyperpolarization was prevented by precontracting the preparations with KCl, no significant differences were found in relaxations to ACh among the study groups. In conclusion, release of cyclooxygenase-derived constricting factors appeared to be more pronounced in male than in female SHR. In addition, the relative role of NO in endothelium-dependent arterial relaxation seemed to be higher in female than in male SHR, and relaxation induced by an NO donor also was more pronounced in female than in male SHR.
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PMID:Influence of gender on control of arterial tone in experimental hypertension. 968 91

Endothelial dysfunction has been reported to be a feature of hypertension. We have investigated the relative contributions of nitric oxide (NO) and the endothelium-derived hyperpolarizing factor (EDHF) to endothelium-dependent relaxations in isolated mesenteries from (mREN-2)-27 transgenic hypertensive (TGH) rats and their normotensive controls (Hannover Sprague-Dawley). Relaxation to the endothelium-dependent relaxant, carbachol, was unimpaired in mesenteries from TGH rats compared to the Hannover Sprague-Dawley controls. Inhibition of NO synthase (with 100 microM Nomega-nitro-L-arginine methyl ester) had greater inhibitory effects against these relaxations in the mesenteries from Hannover Sprague-Dawley compared to TGH. Inhibition of EDHF activity with high K+ also had greater inhibitory effects against endothelium-dependent relaxations in the mesenteries from the Hannover Sprague-Dawley compared to TGH. The present results show that, although endothelium-dependent relaxation is unimpaired in mesenteries from TGH rats, there are differences in the relative contributions of NO and EDHF, such that inhibition of either NO or EDHF alone in TGH mesenteries has less impact compared to Hannover Sprague-Dawley. It is suggested that the recently identified reciprocal relationship between NO and EDHF is upregulated in the mesenteries from the TGH rats.
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PMID:Characterization of endothelium-dependent relaxations in mesenteries from transgenic hypertensive rats. 980 66

Endothelial dysfunction is increasingly recognized as an early event in the pathogenesis of cardiovascular disease. This observation is consistent with the growing appreciation of the role of endothelium in maintaining cardiovascular health. Endothelial dysfunction and coronary artery disease are both linked to hypertension, hypercholesterolemia, diabetes mellitus, and cigarette smoking. Modification of these conditions improves both endothelial function and coronary artery disease outcomes. Dietary and lifestyle modifications and antioxidant vitamin supplementation have a beneficial effect on endothelial function, as do angiotensin-converting enzyme inhibitors and lipid-lowering agents. Future studies will determine whether interventions that specifically target endothelial dysfunction can reduce rates of clinical disease.
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PMID:Clinical implications of endothelial dysfunction. 1037 88

Endothelial dysfunction appears to be a key early event in a number of important cardiovascular disease states, including atherosclerosis and hypertension. Testing endothelial function in vivo has proved challenging. Although the endothelium releases a number of products, no single blood test has yet proved useful to determine normal endothelial function or early abnormalities. The most common test of endothelial function used to date in vivo depends on measuring endothelium-dependent dilatation in response to pharmacologic or physiologic stimuli. This depends mostly on the endothelial ability to release nitric oxide (NO), not only a potent vasodilator but also an inhibitor of platelet aggregation, monocyte adhesion, and smooth muscle proliferation. Over the past decade, endothelium-dependent dilatation has been tested using high-resolution external vascular ultrasound. The major advantage of this method is that it is completely noninvasive, accurate, and reproducible. The major disadvantage is that the coronary arteries cannot be imaged directly with ultrasound, and therefore the test is usually applied to peripheral arteries, such as the brachial or femoral conduit vessels. Using such ultrasound techniques, many groups have documented endothelial dysfunction in children and young adults at risk for atherosclerosis and have performed a variety of studies concerning reversibility of early arterial damage, using potentially important antiatherogenic strategies.
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PMID:Testing endothelial function using ultrasound. 988 44

Endothelial dysfunction is a feature of the early stages of atherosclerotic cardiovascular disease. It also is almost invariably associated with recognized cardiovascular risk factors, including those that are irreversible (such as age and family history) and those that are reversible (such as hypertension and hypercholesterolemia). It remains the subject of debate whether endothelial dysfunction can be considered an independent risk factor or, perhaps more plausibly, an intermediate or surrogate end point. However, although the relevance to research into cardiovascular pathophysiology is not in dispute, there remains uncertainty about its relevance as a therapeutic target. Overall, the available evidence suggests that targeting of the conventional major risk factors remains the primary strategy, but an ancillary effect on intermediate end points, such as an improvement or reversal of endothelial dysfunction, constitutes an additional potential benefit.
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PMID:Endothelial dysfunction in cardiovascular disease: risk factor, risk marker, or surrogate end point? 988 52

The vascular endothelium plays a key role in the local regulation of vascular tone by the release of vasodilator substances (i.e. endothelium-derived relaxing factor (EDRF = nitric oxide, NO) and prostacyclin) and vasoconstrictor substances (i.e. thromboxane A2, free radicals, or endothelin). Using either agents like acetylcholine or changes in flow to stimulate the release of EDRF (NO), clinical studies have revealed the importance of EDRF in both basal and stimulated control of vascular tone in large epicardial coronary arteries and in the coronary microcirculation. The regulatory function of the endothelium is altered by cardiovascular risk factors or disorders such as hypercholesterolemia, chronic smoking, hypertension or chronic heart failure. Endothelial dysfunction appears to have detrimental functional consequences as well as adverse longterm effects, including vascular remodelling. Endothelial dysfunction is associated with impaired tissue perfusion particularly during stress and paradoxical vasoconstriction of large conduit vessels including the coronary arteries. These effects may cause or contribute to myocardial ischemia. Several mechanisms may be involved in the development of endothelial dysfunction, such as reduced synthesis and release of EDRF or enhanced inactivation of EDRF after its release from endothelial cells by radicals or oxidized low-density lipoprotein (LDL). Increased plasma levels of oxidized LDL have been noted in chronic smokers and are related to the extent endothelial dysfunction, raising the possibility that chronic smoking potentiates endothelial dysfunction by increasing circulating and tissue levels of oxidized LDL. In heart failure, cytokines and/or reduced flow (reflecting reduced shear stress) may be involved in the development of endothelial dysfunction and can be reversed by physical training. Other mechanisms include an activated renin-angiotensin system (i.e. postmyocardial infarction) with increased breakdown of bradykinin by enhanced angiotensin converting enzyme (ACE) activity. There is evidence that endogenous bradykinin is involved in coronary vasomotor control both in coronary conduit and resistance vessels. ACE inhibitors enhance endothelial function by a bradykinin-dependent mechanism and probably also by blunting the generation of superoxide anion. Endothelial dysfunction appears to be reversible by administering L-arginine, the precursor of nitric oxide, lowering cholesterol levels, physical training, antioxidants such as vitamin C, or ACE inhibition.
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PMID:Endothelial dysfunction in human disease. 1007 15

Endothelial dysfunction appears to be an integral aspect of the insulin resistance syndrome, independently of hyperglycemia. The ability of insulin to cause endothelium-derived nitric oxide (NO)-dependent vasodilation amplifies its overall effect of stimulating skeletal muscle glucose uptake and modulating vascular tone. The dose-dependent physiologic increase in skeletal muscle blood flow in response to insulin, which is highly associated with the rate of glucose metabolism, is impaired in insulin-resistant states. Insulin appears to mediate vasodilation by direct stimulation of release of NO from endothelium. Studies of the response to the endothelium-dependent vasodilator methacholine chloride in lean and obese nondiabetic subjects and obese subjects with type 2 diabetes mellitus indicate that there may be marked endothelial dysfunction very early in insulin resistance. The potent vasoprotective effects of NO mitigate various atherogenic processes, including vascular smooth muscle cell proliferation, platelet adhesion and thrombogenesis, lipid peroxidation, and monocyte adhesion to endothelial cells. The interaction between insulin and NO may contribute to the prominent outcomes of insulin resistance syndrome (viz., hypertension, thrombosis, and atherosclerosis).
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PMID:Vascular reactivity. 1041 55

Spontaneously hypertensive rats (SHR) begin to die from cardiovascular complications at approximately 15 months of age. We tested whether chronic ACE-inhibitor treatment would extend the lifespan of such old animals. We also studied cardiac hypertrophy and function, endothelial function and expression, and activity of NO synthase (eNOS). One hundred 15-month-old SHR were randomized into 3 groups, control (n=10), placebo-treated (n=45), and ramipril-treated with an antihypertensive dose of 1 mg. kg(-1). d(-1) in drinking water (n=45). Ex vivo experiments were performed after 15 months (control) and 21 months, when approximately 80% of the placebo group had died. Late treatment with ramipril significantly extended lifespan of the animals from 21 to 30 months. Fully established cardiac hypertrophy, observed in placebo-treated animals and in controls, was significantly reversed by ramipril treatment. In isolated working hearts, a significantly improved function associated with increased cardiac eNOS expression was seen versus placebo and control hearts. Endothelial dysfunction in isolated aortic rings from control and placebo-treated SHR was significantly improved by ACE inhibition and associated with enhanced NO release. Late treatment of SHR with the ACE inhibitor ramipril extended lifespan from 21 to 30 months, which is comparable to the lifespan of untreated normotensive Wistar-Kyoto rats. This lifespan extension, probably due to blood pressure reduction, correlated with increased eNOS expression and activity followed by a regression of left ventricular hypertrophy and cardiac and vascular dysfunction.
Hypertension 1999 Aug
PMID:Late treatment with ramipril increases survival in old spontaneously hypertensive rats. 1045 56

Endothelial dysfunction, as observed in hypertension and atherosclerosis, is associated with a reduction in the bioavailability of endothelium-derived nitric oxide (NO). We tested the hypothesis that alterations in the soluble guanylyl cyclase (sGC) pathway may also contribute to the pathogenesis of hypertension. Therefore, we investigated the expression and activity of sGC in young (6 weeks) and aging (17 months) spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Endothelium-independent relaxation of aortic rings in response to the sGC activator YC-1 was attenuated in SHR, and expression of both alpha(1) and beta(1) subunits of heterodimeric sGC and the basal contents of cGMP were reduced specifically in SHR aorta. Moreover, mRNA expression of the cGMP receptor and effector protein cGMP-dependent protein kinase type Ialpha (cGKIalpha) was also reduced. Interestingly, downregulation of both sGC and cGKIalpha expression was observed in young, ie, normotensive SHR, whereas impairment of the endothelium-independent relaxation was found only in aging SHR. Accordingly, similar cGMP levels were reached in response to YC-1 in young SHR and young WKY, suggesting a compensatory increased sensitivity or effectiveness of the sGC pathway in young SHR. In aging SHR, however, increased sensitivity to YC-1 no longer compensated for the impairment of endothelium-independent relaxation, suggesting that other mechanisms were involved. In fact, endothelium-independent relaxations were partially restored by superoxide dismutase, suggesting a pathophysiological role of superoxide production, particularly at later disease stages. Thus, tissue-specific downregulation of components of the sGC/cGMP pathway is an early event in the pathogenesis of hypertension.
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PMID:Downregulation of soluble guanylyl cyclase in young and aging spontaneously hypertensive rats. 1048 56

The endothelium is an important regulator of coronary vascular tone due to its ability to release potent vasoactive substances such as the vasodilators nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), prostacyclin (PGI2) and the potent vasoconstrictor endothelin. Endothelial dysfunction has been associated with a number of pathological states such as atherosclerosis, hypertension, diabetes and congestive heart failure. A disturbance of endothelial function may also contribute to the adverse effects that ischaemia and reperfusion exerts on the coronary vasculature. After ischaemia and reperfusion there is usually a selective impairment of endothelium-dependent relaxation in isolated coronary arteries. However, in the intact coronary circulation, there is a general loss of vasodilator reserve as responses to both endothelium-dependent and endothelium-independent agonists are attenuated. The release of vasoconstrictor(s) and plugging of capillaries with leukocytes may contribute to that impairment of the capacity of the coronary circulation to dilate together with the reduction in basal blood flow (no-reflow phenomenon). Ischaemic preconditioning is able to prevent ischaemic damage to the myocardium but the vasculature is less well protected as reperfusion is enhanced but the vasodilator reserve continues to be limited. Pharmacological preservation of vascular function has proved more successful with inhibitors of leukocyte adhesion, calcium channel blockers, endothelin receptor antagonists and inhibitors of oxygen radical generation all offering protection. Further refinement of protocols to preserve endothelial and vascular function after ischaemia will aid reperfusion, enhance vasodilator reserve and maximise recovery of myocardial function.
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PMID:Approaches to the prevention of coronary vascular dysfunction caused by myocardial ischaemia and reperfusion. 1060 62


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