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

The effect of vascular endothelium, endocardium, and coronary endothelium on vascular tone and myocardial contraction-relaxation sequence in heart failure is discussed. Vascular endothelium affects underlying vascular smooth muscle through paracrine secretion of relaxing and constricting factors. In heart failure, systemic vasoconstriction results not only from neuroendocrine activation, but also from disturbed local endothelial control of vascular tone because of impaired endothelial-dependent vasodilation and because of increased plasma concentration of endothelin. Experimental evidence obtained in isolated cardiac muscle strips established the influence of endocardial endothelium on the duration of myocardial contraction and on the onset of myocardial relaxation. By analogy to vascular endothelium, both diffusible agents that abbreviate (endothelial-derived relaxation factor-like substance) and those that prolong (endocardin) myocardial contraction have been shown to be released from the endocardium. Similar agents are released from the coronary endothelium and, because of the close proximity of capillaries and myocytes, could exert a major effect on myocardial performance. Endothelial dysfunction and concomitant lack of release of myocardial relaxant factors could explain left ventricular relaxation abnormalities observed in the cardiac allograft or in arterial hypertension. Since endothelial-derived relaxation factor or nitric oxide mediates the coronary reactive hyperemic response, a negative inotropic action of nitric oxide could contribute to left ventricular failure when left ventricular wall stress is elevated, as occurs after myocardial infarction in the noninfarcted zone and during left ventricular volume or pressure overload in the absence of adequate hypertrophy.
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PMID:Endothelial control of vascular and myocardial function in heart failure. 794 59

Our appreciation of the vascular endothelium has changed considerably over the last decade. This organ, finally recognized as such, participates actively in vasomotor regulation and haemostasis. It secretes several relaxing and contracting factors which act locally to determine resting vascular tone. One of the relaxing factors, EDRF/NO plays an important physiological role as it contributes to the rapid adaptation of blood flow to various pharmacological and mechanical stimuli, thereby ensuring maintenance of adequate tissue perfusion. Nitric oxide (NO) is an ubiquitous factor which was crowned "molecule of the year 1992" by the scientific review Science. Its effects extend well beyond those on the cardiovascular system. Endothelial dysfunction is observed in many pathological states such as atherosclerosis, reperfusion injury, postangioplasty endothelial regeneration, degeneration of venous bypass grafts, pure spastic angina, hypertension and diabetes. It is associated with decreased production of EDRF/NO, which probably contributes significantly to the aggravation of endothelial and parietal lesions and to the natural progression of atherosclerotic disease in general. This article describes the principal vasoactive factors secreted by the endothelium and goes on to list the physiologic cardiovascular effects of EDRF/NO in detail, and to review the different pathologies associated with a disorder of secretion of this factor.
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PMID:[EDRF/NO and endothelial functions]. 801 Aug 61

The endothelium regulates vascular tone by releasing factors involved in relaxation and contraction, in coagulation and thrombus formation, and in growth inhibition and stimulation. Endothelium-dependent relaxations are elicited by transmitters, hormones, platelet substances, and the coagulation system, and by physical stimuli such as the shear stress from circulating blood. They are mediated by the endothelium-derived relaxing factor, recently identified as nitric oxide, which causes vasodilation and platelet deactivation. Other proposed endothelium-derived relaxing factors include a hyperpolarizing factor, lipooxygenase products, and the cytochrome P450 pathway. Endothelium-derived contracting factors are produced by the cyclooxygenase pathway and by endothelial cells, which produce the peptide endothelin-1, a potent vasoconstrictor that under normal conditions circulates at low levels. The endothelium produces both growth inhibitors--normally dominant--and growth stimuli. Denuded or dysfunctional endothelium leads to a proliferative response and intimal hyperplasia in the vessel wall; moreover, platelets adhere to the site and release potent growth factors. Endothelial dysfunction has numerous causes: Aging is associated with increased formation of contracting factor and decreased relaxing factor; denudation, such as by coronary angioplasty, impairs the capacities of regenerated endothelial cells; oxidized low-density lipoproteins and hypercholesterolemia interfere with nitric oxide production; hypertension morphologically and functionally alters the endothelium; and atherosclerosis markedly attenuates some endothelium-dependent relaxations. For patients with coronary bypass grafts, differences in endothelium-derived vasoactive factors between the internal mammary artery and the saphenous vein may be important determinants of graft function, with the mammary artery having more pronounced relaxations than the saphenous vein and thus a higher patency rate.
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PMID:Endothelial regulation of vascular tone and growth. 839 13

We examined whether coronary risk factors and atherosclerotic lesions in the study artery were associated with impaired endothelium-dependent dilation of coronary resistance arteries. Acetylcholine (ACH) at graded doses (1, 3, 10 and 30 micrograms/min) and papaverine (10 mg) were selectively infused into the left anterior descending coronary artery of 28 patients, in whom the study artery was angiographically normal (n = 16) or with mild stenosis < or = 40% (n = 12). Coronary blood flow (CBF) was estimated from the product of mean CBF velocity measured by an intracoronary Doppler catheter and the arterial cross-sectional area of the study artery determined by quantitative arteriography. ACH increased CBF in a dose-dependent manner. However, the maximum CBF response to ACH varied widely among patients (from 50% to 660%). By multivariate analysis, the presence of atherosclerotic lesions in the study artery was an independent predictor for impaired CBF response to ACH (P < 0.01). Hypertension (P < 0.001), hypercholesterolemia (r = -0.52, P < 0.005), age > or = 50 yr (P < 0.01) and total number of coronary risk factors (r = -0.62, P < 0.001) were associated with the impaired increase in CBF with ACH by univariate analysis. The percent increase in CBF evoked with papaverine did not correlate with these risk factors. The results suggest that mild atherosclerotic lesions in the study artery and coronary risk factors are accompanied by impaired endothelium-dependent dilation of coronary resistance arteries evoked with ACH. Endothelial dysfunction of coronary resistance arteries may result in altered regulation of myocardial perfusion in patients with mild coronary atherosclerosis and coronary risk factors.
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PMID:Impaired coronary blood flow response to acetylcholine in patients with coronary risk factors and proximal atherosclerotic lesions. 842 26

Endothelial dysfunction is recognized as a critical event in the etiology of cardiovascular diseases, but its possible role during aging in arterial hypertension remains poorly defined. We evaluated the response of aortic rings precontracted with 0.1 microM norepinephrine (NE) to acetylcholine (ACh) in the San Juan hypertensive rats (SJH-Rs) (F19, F20) and Munich Wistar rats (MW). SJH-Rs is a model of inbred salt-sensitive hypertension, whereas similarly treated inbred MW rats are their normotensive counterpart. These experiments were performed with adult (6-7 months) and aged (11-13 months) rats to assess the effects of age and hypertension on endothelium-dependent relaxation. We generated dose-response curves by adding cumulative doses of ACh from 1.0 nM to 10.0 microM. In addition, we evaluated the Ca(2+)-dependent nitric oxide synthase (NOS) activity by increasing cell calcium with the ionophore A23187. The results indicate that hypertension induces a displacement to the right of the dose-response curve to ACh in both adults and aged SJH-Rs; IC50 for adult rats was 0.72 +/- 0.3 microM for SJH-Rs and 0.059 +/- 0.03 microM for MW (p < 0.05). Aged animals showed similar results: IC50 of 0.78 +/- 0.03 microM for SJH-Rs and of 0.043 +/- 0.01 microM in age-matched MW rats (p < 0.025). However, no difference was observed between hypertensive (SJH-Rs) adult and aged animals. Similarly, no difference was observed between adult and aged MW control animals. The displacement of the dose-response curve to ACh in SJH-Rs appears to be associated with a reduced activation of NOS since in precontracted aortas from aged animals 1 microM A23187 induced a relaxation of 51.2 +/- 12% in MW as compared with 34.4 +/- 7% in SJH-Rs (n = 5, p < 0.05). These results indicate that endothelial dysfunction exists in SJH-Rs. The data suggest that an alteration of the endothelial NOS may be the cause of this abnormality. Finally, the magnitude of the endothelial dysfunction is not age dependent within the range evaluated.
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PMID:Endothelial dysfunction in the San Juan hypertensive rat: possible role of the nitric oxide synthase. 876 46

1. Endothelial cells release nitric oxide (NO) and the putative endothelium-derived hyperpolarizing factor (EDHF) in response to an increase in shear stress and receptor stimulation. 2. Tests of endothelial function have principally used acetylcholine (ACh)-mediated relaxation of precontracted isolated blood vessels or increases in forearm blood flow measured by venous occlusion plethysmography. Basal NO release is tested by a rise in resistance during infusion of the NO synthase inhibitor L-NMMA. Potential traps for investigators looking to evoke endothelial dysfunction following reduced ACh responses are discussed. 3. Endothelial dysfunction appears to occur in large but not small arteries in human and animal hypertension. Patients with long-standing congestive heart failure have endothelial dysfunction in buttock skin resistance arteries and there is coronary artery endothelial dysfunction following coronary ischaemia. 4. Remodelled arteries from neointimal thickening as a result of coronary collateral development in dog heart and new angiogenic vessel growth following large artery occlusion in the rabbit hindlimb appear to have normal endothelial function in relation to NO release. 5. Development of specific NO synthase inhibitors, antagonists of EDHF and the constrictor peptide endothelin, will clarify the role of these endothelium-derived factors in the cause or maintenance of vascular dysfunction. Defining redundancy and hierarchy of importance of these vascular factors are areas for future resolution.
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PMID:Role of the endothelium in the genesis of cardiovascular disease. 888 8

1. We measured endothelium-dependent and independent dilatation of forearm resistance arteries in 29 men with diet-treated non-insulin-dependent diabetes mellitus and 18 age- and sex-matched control subjects. None of the diabetic patients had hypercholesterolaemia, overt hypertension or microproteinuria. 2. We examined endogenous and exogenous nitric oxide-mediated vasodilatation by measuring forearm blood flow with venous occlusive plethysmography after administration of acetylcholine (7.5 and 15 micrograms/min) and sodium nitroprusside (3 and 10 micrograms/min), respectively, into the brachial artery. NG-monomethyl-L-arginine was also infused to study the inhibition of basal and stimulated release of nitric oxide. 3. The vasodilatory response to acetylcholine, expressed as area under curve, was significantly decreased in the diabetic patients compared with the control subjects (P = 0.019). NG-monomethyl-L-arginine significantly reduced basal (P < 0.001) and acetylcholine-stimulated blood flow (P < 0.02) in both groups. The vasodilatory response (also expressed as area under curve) to sodium nitroprusside was significantly less (P = 0.044) in the diabetic patients than in the control subjects. 4. In the diabetic patients, impaired vasodilatory responses to acetylcholine were significantly correlated with higher serum triacylglycerols (P = 0.048) and lower high-density lipoprotein-cholesterol concentrations (P = 0.007); the association with high-density lipoprotein was independent of age, glycated haemoglobin and blood pressure. Sodium nitroprusside responses were not correlated with lipid and lipoprotein concentrations. 5. We conclude that there is impaired endothelial and smooth muscle cell function in men with diet-treated non-insulin-dependent diabetes mellitus uncomplicated by overt hypertension or microproteinuria. Endothelial dysfunction may be related to diabetic dyslipidaemia and associated metabolic disturbances.
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PMID:Impaired endothelium-dependent and independent dilatation of forearm resistance arteries in men with diet-treated non-insulin-dependent diabetes: role of dyslipidaemia. 894 95

Recent insights into the pathogenesis of vascular disease have opened up a new frontier that has implications for future therapies. The vasculature has been redefined as a vital organ that can regulate its own tone and structure via numerous cellular mechanisms. The endothelium plays the role of gatekeeper in this process, sensing and responding to stimuli and activating various vasoactive systems that function as mediators. Locally generated vasoactive substances such as angiotensin II and nitric oxide appear to be important determinants of vessel function and structure. Vasoactive substances generated within the endothelium influence cell proliferation and cell death in a complex interplay that, when disturbed, can result in structural alteration known as vascular remodeling. Normal vascular homeostasis is maintained by a balance between vasoconstrictors such as angiotensin II and vasodilators such as nitric oxide. Endothelial dysfunction involves an imbalance between vasoactive substances such that perturbations in the regulation of tone, hemostasis, and vessel structure result in the development of cardiovascular diseases, such as hypertension, atherosclerosis, and heart failure.
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PMID:Endothelial function as a determinant of vascular function and structure: a new therapeutic target. 912 14

1. The present review covers two aspects of the author's research into the pharmacology of vascular reactivity of isolated vessels and in the intact circulation. First, how 'normal' reactivity is altered by injury or disease and, second, how novel drugs have allowed insight into the role of the cotransmitter neuropeptide Y and 'N' type calcium channels in neurotransmitter release. 2. Acute endothelium removal in the femoral artery of the anaesthetized dog confirmed the obligatory role of these cells in the dilatation response to intra-arterial acetylcholine (ACh). After 4 weeks, conduit arteries respond with a thickened neointima following acute endothelial injury but, provided macrophage-derived foam cells are absent, the artery relaxes normally to ACh. 3. In the dog coronary vasculature, stable collateral arteries have a marked neointima of non-contractile smooth muscle cells that are lined with endothelium. Reactivity to vasodilator stimuli is normal while that to vasoconstrictor stimuli is impaired. 4. In the conscious rabbit, superficial femoral artery (SFA) occlusion stimulates profound angiogenesis but, despite these changes to the hindlimb vasculature, reactivity to vasodilator and vasoconstrictor agents from day 1 to 6 months following SFA is unaltered. 5. Endothelial dysfunction is discussed in relation to hypertension, hypercholesterolaemia and congestive heart failure. 6. The novel "N' type calcium channel antagonist omega-conotoxin GVIA, was used to explore the role of "N' type channels in cardiac and vascular neurotransmitter release in conscious rabbits. 7. The novel putative Y 1-selective neuropeptide Y antagonist 1229U91 was shown to inhibit nerve-mediated contractions of isolated mesenteric, but not femoral, artery segments in the rat. This regional difference in a possible cotransmitter role of the peptide is discussed.
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PMID:New insights into vascular reactivity: from altered structure to neural control. 914 77

Our goal was to determine whether environmental tobacco smoke causes endothelial dysfunction in the absence of hypercholesterolemia and whether such an effect can be prevented by supplementation with L-arginine. Environmental tobacco smoke exposure is associated with an increase in coronary artery disease events and mortality. We have previously demonstrated that environmental tobacco smoke causes endothelial dysfunction and atherosclerosis in rabbits with diet-induced hypercholesterolemia and atherosclerosis and that chronic dietary L-arginine supplementation prevents this. The effects of L-arginine supplementation (2.25% solution ad libitum) and environmental tobacco smoke (smoking chambers for 10 weeks) were examined with a 2 x 2 design in 32 rabbits fed a normal diet. Acetylcholine, calcium ionophore A23187, and nitroglycerin-induced vasorelaxation were assessed in aortic rings precontracted with phenylephrine. Endothelial L-arginine levels were measured by chromatography. Chronic L-arginine supplementation increased serum (P < .001) and endothelial (P = .003) L-arginine levels. Environmental tobacco smoke reduced endothelium-dependent acetylcholine-induced relaxation, and L-arginine blocked this adverse effect (P = .04). Environmental tobacco smoke tended to increase phenylephrine-induced contraction (P = .06). Neither environmental tobacco smoke nor L-arginine influenced A23187-induced relaxation nor endothelium-independent nitroglycerin-induced relaxation. Endothelial dysfunction secondary to environmental tobacco smoke may occur in the absence of diet-induced hypercholesterolemia and atherosclerosis. Chronic dietary supplementation with a nitric oxide donor such as L-arginine offsets the endothelial dysfunction associated with environmental tobacco smoke in normocholesterolemic rabbits, possibly through substrate loading of the nitric oxide pathway.
Hypertension 1997 May
PMID:Chronic dietary L-arginine prevents endothelial dysfunction secondary to environmental tobacco smoke in normocholesterolemic rabbits. 914 85


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