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

Old concepts of an "inert" vascular endothelium have been entirely discredited. It is now known that the vascular endothelium and media form a "functional unit", communicating via both electric and humoral signals. Normal endothelium maintains vascular dilation through release of various dilatory substances, the main one being endothelial relaxing factor (EDRF), which is nitric oxide (NO). EDRF is, for example, released in response to increased shear stress that accompanies high flow rates, and acts by engaging the cyclic GMP system of smooth muscle cells. Even potential vasoconstrictors such as vasopressin, catecholamines and serotonin release EDRF. Endothelial release of prostacyclin supplements the EDRF action. EDRF (and prostacyclin) also inhibit platelet aggregation. In the presence of hypertension and/or atherosclerosis, endothelial function is often impaired and pressor/thrombogenic factors such as endothelin, thromboxane, vasopressin, catecholamines, and serotonin become more dominant. Antihypertensive therapy should, ideally, seek to restore endothelial function to normal.
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PMID:Hypertension and endothelial function--aspects of atheroma protection. 134 64

This study was performed to determine whether structural changes in cerebral arterioles could account for differences in susceptibility of the blood-brain barrier to acute hypertensive disruption between hypertensive and normotensive animals. We studied spontaneously hypertensive rats (SHR), 3 other models of hypertension and their normotensive controls. The age and duration of hypertension of the rats were matched to an earlier study showing that protection of the blood-brain barrier was usually found in rats with chronic hypertension. We measured the dimensions of fixed pial arterioles and minimal cerebrovascular resistance produced by bicuculline. Minimal cerebrovascular resistance was not different between the groups of animals. There were no differences in the area of the media of pial arterioles between any of the groups. In addition, we examined the possibility that sympathetic nerves might affect cerebrovascular resistance during bicuculline in SHR. The presence of sympathetic nerves in SHR, but not WKY, reduced the degree of cerebral vascular dilation during bicuculline. From these data we conclude that 1) structural changes in cerebral vessels do not account for protection of the blood-brain barrier in rats with a moderate duration of hypertension and 2) sympathetic nerves may have an exaggerated effect on cerebral vessels of SHR.
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PMID:Hypertension and cerebral arteries: relationship to disruption of the blood-brain barrier. 234 97

This review compares the calcium antagonists with diuretics in the management of mild-to-moderate essential hypertension. The antihypertensive efficacy of calcium antagonists appears comparable to that of oral diuretics such as hydrochlorothiazide when used as monotherapy. Peripheral vascular dilation appears to be the principal mechanism of the long-term blood pressure-lowering effects of both calcium antagonists and diuretics. Peripheral vasoconstrictor responses to cardioreflex-mediated sympathetic nervous system activation is attenuated by calcium antagonists but not by diuretics. Long-term calcium antagonist therapy is generally not associated with reflex activation of the sympathetic nervous system or of the renin-angiotensin-aldosterone axis, whereas diuretic therapy results in considerable activation of the renin-angiotensin-aldosterone system. Calcium antagonists appear to have a greater beneficial effect than diuretics with respect to maintenance of renal blood flow and glomerular filtration rate. Calcium antagonists, because of their effects on coronary blood flow and heart rate-blood pressure product, offer advantages over diuretics in the treatment of hypertensive patients with concomitant ischemic heart disease. Metabolic abnormalities associated with diuretic antihypertensive therapy, such as hypokalemia, hypercalcemia, hyperuricemia, lipid changes, and hyperglycemia, are generally not observed with calcium antagonists. Many of these deleterious metabolic changes observed with diuretic therapy may be minimized by the use of smaller doses of these agents than have generally been employed in the past. Diuretics are less expensive and require less frequent dosing than calcium antagonists. Thus, they continue to be preferable first-line antihypertensive agents in many patients with mild-to-moderate hypertension.
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PMID:Comparison of calcium-entry blockers and diuretics in the treatment of hypertensive patients. 355 13

Calcium antagonists, of which the best known are verapamil, nifedipine and diltiazem, are a powerful group of cardioactive agents with a clinical spectrum of indications rather similar to those of beta-adrenoceptor blockade, including angina of effort, angina at rest, hypertension and supraventricular tachycardias (nifedipine is ineffective for the latter). In angina caused by coronary spasm, calcium antagonists are preferred to beta-blockade. Calcium antagonists have a basically different mode of action from beta-adrenoceptor blockade, although both ultimately act on the free cytoplasmic calcium ion concentration. Critical differences between the calcium antagonists are dependent on the individual properties of the calcium antagonists concerned. Different binding sites on the sarcolemma have been identified for nifedipine-like agents and verapamil, but with a different interaction with the nifedipine site. None of these sites might be relevant to the binding of calcium antagonists to the tissue of their therapeutic site of action (arterial smooth muscle for all; atrioventricular node for verapamil and diltiazem). As a group, calcium antagonists cause vascular dilation and do not cause bronchial constriction, in contrast to the beta-adrenoceptor blocking agents. In many patients, these diverse properties allow safe combination of calcium antagonists and beta-adrenoceptor blockers if due care is observed, especially in the case of nifedipine. The clinical differences between the effects of various calcium antagonists reflect: (i) the greater vasodilator capacity of nifedipine, so that at a given concentration the afterload effect dominates over possible effects on the nodal or myocardial tissue; (ii) the greater inhibition of vagal tone by nifedipine than by verapamil or diltiazem; and (iii) the greater inhibition of the atrioventricular node by verapamil and diltiazem. In angina of effort, calcium antagonists are now becoming the agents of first choice in some centers. Experimental use of calcium antagonists include the possible prevention of ventricular fibrillation, the inhibition of ischemic injury, the prevention of catecholamine mediated injury to the myocardium and decreased arterial calcinosis.
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PMID:Calcium ions, drug action and the heart--with special reference to calcium antagonist drugs. 615 Nov 99

The chief site of action of the calcium antagonist drugs is the slow calcium channel in two tissues: the atrioventricular node and vascular smooth muscle. The exact mode whereby these agents work is still unknown, but recently studies with radioligands suggest that the binding site for the dihydropyridines such as nifedipine is different from the site for the verapamil group (including diltiazem). In some way these agents 'close' or 'block' the calcium channels. Verapamil and diltiazem are active against the calcium channel of the atrioventricular node which nifedipine in clinical doses is not; in contrast, nifedipine is more active on peripheral vascular arterial muscle, presumably inhibiting the calcium channel more strongly. An intracellular site of action of these agents on calmodulin in vascular smooth muscle cannot be excluded. Clinically, the chief calcium antagonists (verapamil, nifedipine, diltiazem) constitute a powerful group of cardioactive agents with a spectrum of therapeutic actions rather similar to beta-adrenoceptor blockade, being effective in angina of effort and rest, and hypertension. Critical differences are dependent on the individual properties of the calcium antagonists. Thus only verapamil and diltiazem are effective in inhibiting the AV node while the dihydropyridines such as nifedipine are only vasodilators in clinical doses. As a group, calcium antagonists cause vascular dilation and do not cause bronchial constriction, in contrast to the beta-adrenoceptor blocking agents. In many patients these diverse properties allow safe combination of calcium antagonists and beta-adrenoceptor blockers if due care is observed.
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PMID:Calcium antagonists. Mechanisms, therapeutic indications and reservations: a review. 632 68

1. The contribution of arteriolar structural change to hindlimb vascular resistance was examined in the renal wrap hypertensive rabbit. 2. Haemodynamic variables were recorded at rest and after maximal vascular dilation using sodium nitroprusside and peripheral autonomic effector blockade. In the same animals at the end of experiments, morphometric measurements of hindlimb muscle arterioles were made. 3. Mean arterial pressure (MAP) and hindlimb vascular resistance were elevated in hypertensive animals compared with normotensive animals at rest and after maximal dilation. 4. Lumen area and lumen diameter were reduced whereas wall area and wall area to lumen area ratio were increased in hypertensive animals compared with normotensive animals. 5. In the renal wrap model of hypertension, the reduction in lumen area of arterioles, < 200 microns in diameter, is sufficient to explain the increase in haemodynamic resistance.
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PMID:Structural influences on resistance in the hindlimb vascular bed of the renal hypertensive rabbit. 832 27

To successfully match the treatment to the cause for raised intracranial pressure (ICP) after a severe head injury, it is important to know the underlying mechanism at a given moment for the raised pressure. In particular, it is important to distinguish between active cerebral vasodilation, indicating functional autoregulation, and a passive vascular dilation as the cause for raised ICP. An experimental study was performed in feline models of diffusely raised ICP (n = 6), of active arterial vasodilation caused by arterial hypercarbia (n = 6), and of passive arterial dilation caused by pharmacologically induced arterial hypertension (n = 6) to determine if wave form analysis of ICP can distinguish active from passive arteriolar vasodilation. Pulsatile pressure transmission from the blood pressure pulse to the ICP pulse (cerebrovascular pressure transmission [CVPT]), cerebrovascular resistance, and craniospinal compliance were measured simultaneously at each level of raised ICP, arterial hypercarbia, and arterial hypertension. Arterial hypercarbia, caused by both 5 and 10% inspired CO2 increased low-frequency CVPT, which was followed by an increasingly negative phase shift between the blood pressure and ICP wave form (P < 0.05). Diffusely raised ICP caused by intraventricular infusion of mock cerebrospinal fluid caused increased low-frequency CVPT (P < 0.01) but resulted in no overall change in phase shift, although the sign of the phase shift remained negative. After arterial hypertension, caused by the infusion of angiotensin II, where there was loss of myogenic tone, an increased low-frequency CVPT was accompanied by a positive phase shift (P < 0.01). These data demonstrate it may be possible to distinguish active arteriolar vasodilation from a passive loss of autoregulatory vascular tone through simultaneous measurement of the low-frequency CVPT and phase shift. Analysis of the ICP wave form provides information relevant to the management of raised ICP.
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PMID:An experimental study of cerebrovascular resistance, pressure transmission, and craniospinal compliance. 812 65

Hypertension is a major healthcare problem afflicting nearly 50 million individuals in the United States. Despite its strong causal association with cardiovascular disease complications including myocardial infarction, heart failure, and stroke, the majority of patients with hypertension do not achieve optimal blood pressure control. The prevalence of hypertension is expected to increase with the aging population, growing obesity epidemic, and rising incidence of metabolic syndrome. Endothelial dysfunction and reduced nitric oxide (NO) bioactivity represent prominent pathophysiological abnormalities associated with hypertensive cardiovascular disease. Individuals with hypertension exhibit blunted epicardial and resistance vascular dilation to endothelium-derived nitric oxide (EDNO) agonists in the peripheral and coronary circulation that likely contributes to mechanisms of altered vascular tone in hypertension. The amino acid L-arginine serves as the principal substrate for vascular NO production. Numerous studies, though not uniformly, demonstrate a beneficial effect of acute and chronic L-arginine supplementation on EDNO production and endothelial function, and L-arginine has been shown to reduce systemic blood pressure in some forms of experimental hypertension. This brief review discusses the potential role of L-arginine in hypertension, and reviews possible mechanisms of L-arginine action including modulation of EDNO production, alteration of asymmetrical dimethylarginine (ADMA):L-arginine balance, and possible improvement of insulin sensitivity. In view of the rising prevalence of hypertension, randomized human clinical studies investigating the potential therapeutic role of L-arginine may be warranted.
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PMID:L-arginine and hypertension. 1546 90

Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal tubules and dilate the renal vasculature, we have examined their effects on renal hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with fenofibrate (30 mg.kg(-1).day(-1) ig) or AUDA (50 mg/l in drinking water) for 2 wk, mean arterial pressure, renal vascular resistance, and glomerular filtration rate were lower but renal blood flow was higher than in vehicle-treated control rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in the HF rats. Treatment with MSPPOH (20 mg.kg(-1).day(-1) iv) + fenofibrate for 2 wk reversed renal hemodynamics and sodium balance to the levels in control HF rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP epoxygenase activity, whereas the fenofibrate-induced elevation of this activity was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced the expression of CYP epoxygenases in renal cortex and microvessels and that the induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA-induced stabilization of EET production in the kidneys cause renal vascular dilation and reduce sodium retention, contributing to the improvement of abnormal renal hemodynamics and hypertension in HF rats.
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PMID:Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats. 1744 29

We studied the effects of antioxidants resveratrol and pQ510 on physiological parameters and the state of endothelial NO-synthase as a marker of the regulatory function of the endothelium in the aorta of rats with modeled arterial hypertension. The antioxidants promoted recovery of stable NO metabolites in rat serum and maintained expression of endothelial NO-synthase at a normal level. These effects were confirmed by correction of blood pressure and endothelium-dependent vascular dilation assessed by endothelial dysfunction coefficient.
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PMID:Effect of antioxidants pQ510 and resveratrol on regulatory function of the endothelium in rats with modeled arterial hypertension. 1823 99


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