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

Angiotensin-converting enzyme inhibitors (CEI) have been found effective in numerous cases of arterial hypertension, even non renovascular, and they are now widely used. However, the reference compound, captopril, has exhibited various side-effects, including acute renal failure. Different mechanisms may be responsible for this complication. In some case haemodynamic changes occur which are rapidly reversible after treatment is discontinued. In other, less frequent cases, captopril induces an immunoallergic interstitial nephritis, sometimes accompanied by skin rashes and/or eosinophilia. Since renal biopsies have been performed in only a few cases of CEI-induced nephropathy, we thought that it might be of interest to report a case of acute renal failure due to acute interstitial nephritis with epithelioid granulomas in the interstitium. The favourable outcome was confirmed by two successive follow-up renal biopsies.
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PMID:[Acute and reversible interstitial granulomatous nephropathy after treatment with captopril]. 209 22

Angiotensin-converting enzyme inhibitor-induced renal failure is now a well-recognized phenomenon that appears to occur almost exclusively in patients with a preexisting reduction in renal perfusion pressure, especially those with renovascular disease. In the latter group of patients, renal failure probably results from some combination of reduced poststenotic renal perfusion pressure and a unique disturbance in the autoregulation of glomerular filtration rate. Although traditionally regarded as functional and reversible, recent animal studies suggest that angiotensin-converting enzyme inhibitor-induced reductions of glomerular filtration rate may lead to progressive renal atrophy, an observation that raises concerns about the long-term safety of these agents in patients with renovascular disease. On the other hand, the deleterious consequences of angiotensin-converting enzyme inhibition in renovascular disease have been exploited as aids in the diagnosis of this disorder. Whether the adjunctive use of angiotensin-converting enzyme inhibitors will prove to be useful in screening large populations of hypertensive patients for renovascular hypertension remains to be determined. However, such adjunctive tests appear to be useful in judging the functional significance of angiographically documented renal artery stenosis.
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PMID:Angiotensin-converting enzyme inhibitor-induced renal failure: causes, consequences, and diagnostic uses. 210 46

When inhibitors of the renin-angiotensin system (RAS) were initially developed, they were believed to act as antihypertensive agents mainly under pathophysiological conditions, in which an elevated plasma RAS contributed to the elevation and maintenance of high blood pressure (BP). However, evidence has accumulated from studies in hypertensive patients, as well as in animals, indicating that BP could be lowered by converting-enzyme inhibitors (CEIs) independently of whether or not the plasma RAS was stimulated. Several other effects had to be considered. It was thus discovered that converting enzyme (CE) is identical with the bradykinin-degrading enzyme, kininase II, and CEIs can therefore potentiate the vasodepressor effects of bradykinin and thereby interact with the prostaglandin system. Actions of CEIs possibly unrelated to inhibition of angiotensin and kininase also need to be considered. The actions of CEIs at the tissue level (brain, heart, blood vessels, kidney, adrenal gland) and their interference with the autonomic nervous system through central and peripheral actions may under certain conditions be more important than their inhibition of the circulating hormonal plasma angiotensin II. Recent clinical and experimental studies and new insights in the molecular biology of the RAS, especially gene expression of renin and angiotensinogen in tissues of the cardiovascular system, support this view. We have found that chronic CE inhibition with substances such as captopril, quinapril and lisinopril specifically affects angiotensinogen mRNA levels in cardiovascular tissues, and has marked effects on left ventricular hypertrophy, possibly through an action on cardiac angiotensin. These findings have consequences not only for the understanding of pharmacokinetics and pharmacodynamics of CEIs but also for their practical therapeutic use.
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PMID:The role of tissue renin-angiotensin systems in hypertension and effects of chronic converting-enzyme inhibition. 216 28

This study was undertaken to verify the activity of plasma kininases in hypertension. Male Wistar rats (WIS) were used and three models of experimental hypertension were studied: spontaneously hypertensive rats (SHR), renal hypertensive rats, made according to the method of Goldblatt, DOCA-salt hypertensive rats. Normal Wistar rats, nephrectomized rats and sodium-loaded rats were used as control groups. Plasma from these animals was used to evaluate the kininase activities: kininase II activity (KII) was measured by the hydrolysis of hippuryl-L-histidyl-L-leucine (HHL); kininase I activity (KI) was measured by the hydrolysis of hippuryl-L-arginine (HLA) (CN1 activity) and of hippuryl-L-lysine (HLL) (CN2 activity). The three enzyme activities were characterized by their kinetic constants and the inhibitory pattern of various inhibitors. In normal WIS rats, hydrolysis of HHL proceeds with a Km of 2.55 +/- 0.22 mM and at a Vmax of 0.357 +/- 0.017 mumol/min/ml; the enzyme is inhibited by EDTA, 0-phenanthroline and captopril. HLA has a Km of 6.93 +/- 0.32 mM and a Vmax of 0.748 +/- 0.019 mumol/min/ml while the Km and Vmax values of HLL are 35.8 +/- 1.52 mM and 13.11 +/- 0.40 mumol/min/ml. The hydrolysis of both substrates is inhibited by EDTA, 0-phenanthroline and MERGETPA. KII activity is decreased in WKY and SHR rats (Vmax = 0.241 +/- 0.014 and 0.262 +/- 0.011 mumol/min/ml, respectively). In renal hypertensive rats and DOCA-salt hypertensive rats, the KII activity remained unchanged. CN1 activity was increased in 1K, 1C hypertensive animals (Vmax = 0.866 +/- 0.221 mumol/min/ml) and in DOCA-salt hypertensive rats (Vmax = 1.119 +/- 0.049 mumol/min/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Activity of plasma kininase I and kininase II in hypertensive rats]. 217 85

The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32 +/- 3 vs. 3 +/- 1 mm Hg, p less than 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25 +/- 4 vs. 26 +/- 2 mm Hg; prostaglandin E2, 48 +/- 3 vs. 47 +/- 8 mm Hg; norepinephrine, 17 +/- 2 vs. 18 +/- 2 mm Hg; leucine-enkephaline, 15 +/- 2 vs. 16 +/- 1 mm Hg; neurotensin, 18 +/- 2 vs. 19 +/- 1 mm Hg; substance P, 19 +/- 2 vs. 19 +/- 2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44 +/- 9 mm Hg (p less than 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22 +/- 6 mm Hg, p less than 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.
Hypertension 1990 Apr
PMID:Brain kinins are responsible for the pressor effect of intracerebroventricular captopril in spontaneously hypertensive rats. 218 Aug 19

Angiotensin-converting enzyme inhibitory therapy is widely used to treat hypertension. With long-term use, it is now being shown to have a beneficial effect on renal function and proteinuria in patients with renal insufficiency. When hypertensive patients with renal insufficiency are treated with enalapril, glomerular filtration rate is maintained, effective renal plasma flow is increased, and microalbuminuria and gross proteinuria are reduced. These beneficial renal changes with enalapril therapy differ from those of most other conventional antihypertensive medications. Clinical awareness of potential problems with hyperkalemia and increasing azotemia, particularly in the setting of salt/volume depletion, is important to assure optimal patient management. When these problems occur, they are nearly always reversible by correcting salt/volume status and/or interrupting enalapril therapy.
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PMID:Long-term renal effects of enalapril therapy in patients with renal insufficiency. 218 74

Hypertension is a major potential problem among the increasing number of older persons in the population, threatening their health and shortening their life expectancy due particularly to stroke and congestive heart failure (CHF). Controlled studies have shown that antihypertensive drug therapy reduces the incidence of severe CHF, stroke and cardiovascular mortality in the elderly. Special consideration should be given to altered drug metabolism, altered responses to drugs, and concomitant medications when pharmacotherapy is instituted in the elderly. Angiotensin-converting enzyme (ACE) inhibitors are acceptable in the hypertensive older patient as first-line therapy for all grades of hypertension and as second-line therapy for the patient with CHF. Use of ACE inhibitors avoids many of the symptoms and metabolic disturbances associated with beta-blockers and diuretics. Quinapril is a new non-sulphydryl ACE inhibitor whose active metabolite, quinaprilat, has a relatively short accumulation half-life compared with enalapril and lisinopril but has an enhanced affinity for the converting enzyme, allowing rapid excretion of the drug while retaining a 24-hour antihypertensive effect with once-daily dosing. Quinapril is a valuable addition to the ACE inhibitor class, with demonstrated efficacy and safety in the older patient.
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PMID:ACE inhibitors in the treatment of hypertension in the older patient. 219 9

The lack of kinin formation in systemic circulation and in the renal system may lead to the pathogenesis of high blood pressure (hypertension). Angiotensin converting enzyme inhibitors are able to protect the kinin inactivation by kininase II, therefore, causing an accumulation of kinin. Although the concentrations of kinin in plasma after oral administration of ACE inhibitors are conflicting this is mainly due to methodological difficulties. Kinin receptor antagonists are becoming most reliable pharmacological probes for defining the molecular actions of kinin in several physiopathological states, and in the mechanism of actions of drugs which are dependent on the kinin system. The blood pressure lowering effect of ACE inhibitors can be antagonized by the pretreatment with kinin receptor antagonists. I have therefore proposed that the hypotensive action of ACE inhibitors may reflect the activation of kinin receptor. It is suggested that the development of compounds having protective properties on the kallikrein-kinin system might be therapeutically applicable as anti-hypertensive drugs.
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PMID:Does kinin mediate the hypotensive action of angiotensin converting enzyme (ACE) inhibitors? 219 99

The increased neuroendocrine activity in patients with congestive heart failure appears to be a generalized attempt to maintain blood pressure at the expense of reduced cardiac performance and salt and water retention. It is likely that baroreceptor dysfunction contributes to increased sympathetic nervous system activity in patients with congestive heart failure. The usual tonic inhibitory messages emanating from baro- and mechanoreceptors in the great vessels and heart fail to adjust sympathetic traffic from the brain to the periphery, leading to uninhibited sympathetic tone. Arginine vasopressin and plasma renin activity may be increased secondarily; however, plasma renin activity activation could also be induced by a low-salt diet and diuretic use. Preliminary baseline data indicate that patients with left ventricular dysfunction (ejection fraction less than or equal to 35%) but no or very mild symptoms of heart failure have increased plasma levels of norepinephrine, atrial natriuretic factor and arginine vasopressin, while plasma renin activity is normal, suggesting that neuroendocrine activity contributes to the pathogenesis of congestive heart failure. Neurohormones such as angiotensin II may alter gene expression, leading to changes in the shape and size of the cell. Remodeling of the heart and blood vessels is associated with both heart failure and hypertension. Angiotensin-converting enzyme inhibitors have been demonstrated to retard or reverse the remodeling process under certain experimental conditions. Studies are currently under way to test this possibility in patients.
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PMID:Neuroendocrine activity in congestive heart failure. 222 Jun 3

Angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers are two classes of antihypertensive agents with novel effects on renal function. In both experimental and clinical studies, calcium channel blockers tend to increase renal blood flow, glomerular filtration rate, and urinary sodium excretion in essential hypertension. ACE inhibitors have similar effects on renal blood flow and glomerular filtration rate in essential hypertension, but they tend to cause sodium retention. ACE inhibitors can cause marked reductions in glomerular filtration rate in renovascular hypertension, making them a problematic choice for the treatment of this form of hypertension. In chronic, progressive renal diseases, ACE inhibitors have been shown to decrease protein excretion and morphologic evidence of glomerulosclerosis. The relationship of the decrease in protein excretion to the progression of renal disease has not yet been established.
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PMID:Calcium channel blockers versus angiotensin-converting enzyme inhibitors: renal effects. 222 Jul 96


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