UMLS:C0085580 - FACTA Search

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Query: UMLS:C0085580 (essential hypertension)
14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angiotensin system exerts a cardinal role in the maintenance of blood pressure and in the regulation of water and sodium excretion through its multiple effects on the vasculature, the kidneys, the heart, the adrenal glands and the brain. Over the last 30 years, blockade of the renin-angiotensin cascade with angiotensin converting enzyme (ACE) inhibitors has proved to be a major advance in the treatment of hypertension and the prevention of its cardiovascular complications. The recent development of specific, orally active angiotensin AT(1) receptor antagonists has provided further insights into the role of the various angiotensin receptor subtypes in the regulation of blood pressure. Even more importantly, these new specific antagonists have provided the opportunity to effectively block the renin-angiotensin system in hypertensive patients with an efficacy comparable to that of other antihypertensive agents but with a tolerability profile similar to that of placebo. Numerous clinical studies have now demonstrated the potential benefits of these agents in the management of essential hypertension. We now need to know whether these agents are capable of reducing the cardiovascular morbidity and mortality associated with hypertension. To this purpose, several large clinical trials are ongoing and we are eager to read their results.
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PMID:[Pathophysiological and clinical implications of AT(1) and AT(2) angiotensin II receptors in essential hypertension]. 1203 86

Angiotensin II receptor antagonists (AAIIs) are the most specific inhibitors of the renin-angiotensin-aldosterone system. There are two types of angiotensin II (Ang II) receptors, the AT(1) receptor, which is responsible for all the classical physiological properties of Ang II, and the AT(2) receptor, whose function in humans remains unclear. The different AAIIs used in clinical practice vary depending on their pharmacodynamic and pharmacokinetic properties, and, for some of them, depending on their metabolism in vivo into an active metabolite. AAIIs are relatively well tolerated, and, unlike angiotensin-converting enzyme inhibitors (ACEIs), do not induce cough. AAIIs are indicated in mild, moderate and severe essential hypertension, where their efficacy has been proven in many studies. The maximal antihypertensive effect is obtained in a few days or weeks, and is somewhat retarded when compared with ACEIs. Their effect is independent of age and sex, but does depend to a certain extent on ethnic origin, since Afro-American patients are less sensitive to AAIIs than Caucasians. In general, the antihypertensive and haemodynamic response to blockers of the renin-angiotensin system is potentiated in presence of a negative salt balance and attenuated in case of a positive salt balance. This means that AAII efficiency is improved by salt depletion induced by a salt-free diet or thiazide diuretics. AAIIs induce short-term improvement of haemodynamic parameters in cardiac insufficiency. Several ongoing clinical trials have been designed to compare their efficacy in cardiac insufficiency and myocardial infarction with those of reference treatments. Valsartan has been recently shown to improve morbimortality in patients with cardiac insufficiency and receiving a conventional treatment including an ACEI. It has been convincingly shown that blockade of the renin-aldosterone system by ACEIs decreases proteinuria and slows down the progression of renal insufficiency, especially in type 2 diabetic nephropathy. Recent trials have shown that AAIIs share the same properties as ACEIs in these indications. It appears that the beneficial effect of AAIIs and ACEIs is not entirely explained by the blood pressure lowering effect of these drugs. AAII administration increases renin release and Ang II production, which may overcome Ang II blockade. On this basis, the combination of an AAII and an ACEI has been proposed to achieve a maximal renin-angiotensin system blockade. Several experimental studies in animals and preliminary clinical studies all indicate that the combination of the two drugs may be more beneficial than either drug used alone in hypertension, cardiac insufficiency and post-myocardial infarction. Clinical trials are necessary to further document the putative advantages of such a combined therapy. The future of AAIIs depends on the following: progress made in the understanding of the molecular and cellular activities of angiotensin (angiotensin receptor signalling, receptor dimerisation, presence of other angiotensin receptor subtypes, role of AT(2) receptor, etc.);a comprehensive view of the role of the local renin system in various organs (local generation and effect of Ang II on cellular proliferation, fibrosis, inflammation, angiogenesis, etc.);predictability of the response to AAII treatment (genetic predisposition to AAII treatment, in conjunction with environmental factors); andresults of the ongoing clinical trials designed to assess the long-term effects of AAIIs in cardiovascular mortality and morbidity, in comparison with reference treatments.
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PMID:[Angiotensin II receptor blockers: current status and future prospects]. 1203 89

Measurement of regional sympathetic activity with nerve recording and noradrenaline spillover isotope dilution techniques demonstrates activation of the sympathetic nerves of the heart, kidneys and skeletal muscle vasculature in younger patients with essential hypertension. Sympathetic overactivity in the renal sympathetic outflow is a prominent pathophysiological feature in obesity-related hypertensives of any age. This increase in sympathetic activity is thought to both initiate and sustain the blood pressure elevation, and, in addition, contributes to adverse cardiovascular events. Sympathetic overactivity seems to particularly influence systolic pressure, by increasing the rate of left ventricular ejection, by reducing arterial compliance through increasing neural arterial tone, and via arteriolar vasoconstriction, by promoting rebound of the reflected arterial wave from the periphery. Inhibition of the renin-angiotensin system in certain circumstances appears to be able to reduce sympathetic nervous activity. Claims have been made for such an action at virtually every site in the sympathetic neuraxis. In reality, renin-angiotensin actions on the sympathetic nervous system are probably much more circumscribed than this, with the case perhaps being strongest for a presynaptic action of angiotensin on sympathetic nerves, to augment noradrenaline release. The ability of angiotensin receptor blockers to antagonize neural presynaptic angiotensin AT1 receptors appears to differ markedly between the individual agents in this drug class. In experimental models, such as the pithed rat, neural presynaptic actions are particularly evident with eprosartan. In a blinded study of crossover design, the effects of eprosartan and losartan on sympathetic nerve firing, measured by microneurography, and whole body noradrenaline spillover to plasma is currently being measured in patients with essential hypertension. A reduction in noradrenaline spillover disproportionate to any possible fall in nerve firing would document the presence of presynaptic antagonism of noradrenaline release.
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PMID:Differentiation in the effects of the angiotensin II receptor blocker class on autonomic function. 1218 59

Left ventricular hypertrophy (LVH) is a major cardiovascular risk factor for morbidity and mortality. It is caused by arterial hypertension, although various hemodynamic and nonhemodynamic factors contribute to its development. Especially, the renin-angiotensin-aldosterone system is involved in the pathophysiology of LVH. The Treatment of Mild Hypertension study demonstrated that in mild essential hypertension, nonpharmacologic treatment is an effective tool for treating LVH. There are at least three major meta-analyses with several thousand patients examining the ability of antihypertensive drugs on the reversal of LVH. The results of these meta-analyses are very consistent. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers achieve significantly better results than b-blockers. The most recently published Losartan Intervention For Endpoint reduction in hypertension study confirmed the superiority of angiotensin receptor blockers against b-blockers in a large-scale prospective trial. It also proves for the first time that regression of LVH is associated with better cardiovascular outcome.
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PMID:Are all antihypertensive drug classes equal in reducing left ventricular hypertrophy? 1237 66

To determine the mechanism of protective vascular effect of angiotensin receptor blocker(ARB), the effect of candesartan on blood pressure(BP), ultrasonographically assessed carotid intima-media thickness(IMT), plasma superoxide dismutase activity (SOD), and lipid peroxides(LPO) were measured, and compared with the effects of diuretics in 20 patients with essential hypertension. Candesartan significantly reduced BP similarly with diuretics. However, IMT was significantly reduced by candesartan, but not by diuretics. Also, candesartan increased SOD, and decreased LPO. There were significant relationship between changes in IMT and SOD, and LPO. These results suggest that protective vascular effect of ARB may be through its effect on angiotensin induced oxidative stress independent of BP reduction.
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PMID:[Protective vascular effect of angiotensin receptor blocker (ARB)]. 1239 1

Although vascular compliance, deltaV/deltaP, is abnormal in essential hypertension and can be improved by antihypertensive drug therapy, it is not clear whether drug-induced changes in compliance are attributable solely to lower achieved blood pressure (BP), and thus equally likely with different drugs possessing similar antihypertensive efficacy. Therefore, we used computerized arterial pulse waveform analysis (CAPWA) to measure capacitive (C1) and oscillatory (C2) components of arterial compliance in essential hypertensive subjects (n = 39) before, and 1 and 3 months after achieving normotensive BP values with administration of either dihydropyridine calcium channel antagonists (CaBl, n = 11), converting enzyme inhibitors (CEI, n = 9), angiotensin receptor blockers (ARB, n = 9), or beta-blockers (BBl, n = 10). Despite equivalent effects on BP (CABL: -19 +/- 4/-15 +/- 2 mm Hg; CEI: -12 +/- 3/-13 +/- 2 mm Hg; ARB: -10 +/- 3/-12 +/- 2 mm Hg; and BBl: -14 +/- 3/-12 +/- 2 mm Hg; P <.005 for each drug v pretreatment), CaBl, CEI, and ARB significantly increased arterial compliance (CaBl: %deltaC1 = 30.0 +/- 5.8, %Delta C2 = 43.7 +/- 23.3; CEI: %deltaC1 = 32.7 +/- 5.4, %deltaC2 = 26.7 +/- 7.1; ARB: %deltaC1 = 36.3 +/- 11.8, %deltaC2 = 43.6 +/- 23.1; P <.01 for CaBl, CEI, and ARB v pretreatment), but BBl did not (%deltaC1 = -3.9 +/- 7.6, %deltaC2 = -7.0 +/- 11.5, P = not significant v pretreatment, sig = 0.01 v other drugs). We conclude that for an equivalent effect on BP, arterial compliance improves after therapy with some, but not all antihypertensive drugs. We hypothesize that a greater clinical benefit may result from the preferential use of drugs that concomitantly improve arterial compliance.
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PMID:Differential effects of antihypertensive drug therapy on arterial compliance. 1246 Jul 7

Prospective comparisons of different drug classes have shown that differences in blood pressure control, rather than differences between drug classes, have the over-riding influence on overall outcome. The same studies have also reinforced the need, in the majority of patients, to use combinations of drugs in order to achieve the target of <140/85 mmHg. By contrast, most patients in routine practice receive single agents and consequently fail to achieve target blood pressure. This failure reflects in part the emphasis in individual studies and subsequent guidelines on comparison of individual drugs. In this article we show how the consistency of both theory and a broad range of evidence permits a didactic approach to combination therapy. Our advice is based on the growing recognition that essential hypertension and its treatment fall into two main categories. Younger Caucasians usually have renin-dependent hypertension that responds well to angiotensin-converting-enzyme inhibition or angiotensin receptor blockade (A) or ss blockade (B). Most other patients have low-renin hypertension that responds better to calcium channel blockade (C) or diuretics (D). These latter drugs activate the renin system rendering patients responsive to the addition of renin suppressive therapy. Coincidence of the initials of these main drug classes with the first four letters of the alphabet permits an AB/CD rule, according to which recommended combinations are one drug from each of the "AB" and "CD" categories of drugs. However, the diabetogenic potential of the older "B" and "D" classes leads us to advise against combining "B" and "D" in older patients, and to recommend "A" + "C" + "D" as standard triple therapy for resistant hypertension.
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PMID:Better blood pressure control: how to combine drugs. 1257 84

The recent Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study was conducted in patients with essential hypertension with electrocardiogram evidence of left ventricular hypertrophy. This showed that losartan compared to atenolol resulted in a significant reduction in the primary endpoint of cardiovascular morbidity and mortality, as well as a greater reduction in electrocardiographically-defined left ventricular hypertrophy. Importantly, this was despite a mean blood pressure reduction which was similar in both groups. Furthermore, the atenolol arm was associated with higher incidence of newly diagnosed diabetics. The LIFE study has firmly confirmed a place for losartan (and other angiotensin receptor blockers) in the management of hypertension. Losartan has also been shown to be effective in diabetics and in patients with atrial fibrillation, as well as in left ventricular hypertrophy regression. This trial also raises the possibility that beta-blockers should perhaps not be used as first-line monotherapy.
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PMID:Implications of the LIFE trial. 1272 Apr 97

The management of essential hypertension has increasingly focused on the use of diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, which lower blood pressure (BP) through effects on blood volume and on the renin-angiotensin system. However, in many individuals these agents, whether given alone or in combination, fail to normalize BP. In such cases it is likely that hypertension is at least partly maintained by pathophysiologic mechanisms other than volume and the renin-angiotensin system, and therefore, that pharmacotherapy directed at other mechanisms is needed. One such form of hypertension is the often overlooked entity of neurogenic hypertension. The purpose of this article is to renew attention to this overlooked entity, to provide a very clinically oriented overview of its possible causes and manifestations, and to discuss the potentially important treatment implications of recognizing this form of hypertension. These implications underscore the need for further clinical and research attention concerning neurogenically mediated hypertension.
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PMID:Neurogenic essential hypertension revisited: the case for increased clinical and research attention. 1455 71

Endothelial dysfunction plays a pivotal role in the development of essential hypertension and its complications. The purpose of this study is to assess the effect of antihypertensive treatment with the angiotensin receptor blocker irbesartan on endothelial function in a group of essential hypertensive patients. Thirty-two untreated hypertensives are examined at baseline and at the end of a six-month period of irbesartan treatment. Endothelium-dependent and -independent responses are determined by measuring changes in forearm blood flow (FBF) by strain gauge plethysmography in response to intrarterial infusions of acetylcholine (endothelium-dependent vasodilation [EDV]), sodium nitroprusside (endothelium-independent vasodilation [EIV]), with and without the addition of the nitric oxide (NO) synthase inhibitor L-NMMA. Plasma endothelin, plasma and urinary nitrates and nitrites, and cyclic GMP are measured at baseline and at the end of treatment. Irbesartan promoted a significant increase in EDV (from 433+/-147% to 488+/-75%; P=0.027) and EIV (from 442+/-130% to 495+/-104%; P=0.041). L-NMMA-induced vasoconstriction was significantly enhanced after irbesartan treatment (relative decrease of FBF from 33.4+/-9.5% to 39.5+/-5.6%; P=0.001). Plasma concentrations of endothelin fell significantly after irbesartan treatment (from 5.78+/-1.86 to 4.16+/-1.52 pg/mL; P=0.001). We concluded that long-term irbesartan treatment enhances both endothelium-dependent and -independent vascular vasodilation capacity. In addition to this non-specific effect, irbesartan restores the vasoconstriction capacity of NO synthase inhibitors, suggesting a direct effect on tonic NO release, and decreases endothelin production. These actions may play an important role in the vascular protecting effects of irbesartan.
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PMID:Effect of long-term irbesartan treatment on endothelium-dependent vasodilation in essential hypertensive patients. 1472 34

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