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

To assess the role of the vascular angiotensin II-generating system in one-kidney, one clip hypertension, we determined the angiotensin converting enzyme activity in plasma and vascular tissues and examined the pressor response to angiotensin II, angiotensin I, and tetradecapeptide renin substrate in isolated mesenteric arteries from one-kidney, one clip hypertensive rats 7 and 30 days after clipping the renal artery and in mesenteric arteries from age-matched normotensive rats. Angiotensin converting enzyme activity, determined in aortic and mesenteric tissues, was significantly augmented in the hypertensive (30 days after clipping) group, whereas plasma activity was normal. The vasoconstrictor responses elicited by angiotensin I and tetradecapeptide in arteries from hypertensive rats were found to be significantly potentiated 30 days after clipping, whereas the angiotensin II responses were basically unchanged. Saralasin completely blocked the vasoconstrictor responses, whereas captopril blocked only the responses to angiotensin I without affecting the responses elicited by angiotensin II and tetradecapeptide. Enalapril, an angiotensin converting enzyme inhibitor given intravenously to unanesthetized rats, significantly lowered the blood pressure of hypertensive rats. The pressor responses elicited by angiotensin II, angiotensin I, and tetradecapeptide were completely inhibited by saralasin, whereas enalapril blocked only the responses of angiotensin I but not those elicited by angiotensin II and tetradecapeptide. These results indicate that local formation of angiotensin II is increased in arteries of one-kidney, one clip hypertensive rats. The data obtained with tetradecapeptide renin substrate suggest an important role for nonrenin proteases in vascular angiotensin II formation.
Hypertension 1992 Jun
PMID:Increased vascular formation of angiotensin II in one-kidney, one clip hypertension. 131 51

Our study attempted to evaluate the importance of changes in the circulating renin-angiotensin-aldosterone system (RAAS) and in hemodynamics in relation to observed changes in cardiovascular structure. We studied previously untreated men (n = 28) with essential nonmalignant hypertension and a supine casual diastolic blood pressure > 95 mm Hg on three to four separate (> 1-week interval) occasions measured in triplicate. We used intraarterial blood pressure, dye-dilution technique, plethysmography (hands), eye-ground photos, M-mode echocardiography, radio immunoassays, and multiple regression analysis. Patients were randomized to 6 months of double-blind treatment with either enalapril or hydrochlorothiazide, following 4 to 6 weeks on placebo. We found that enalapril blocked the plasma angiotensin converting enzyme (ACE) with a secondary increment in plasma renin activity (PRA) and reductions in angiotensin II (AII) and aldosterone. Blood pressure was lowered through a reduction in total peripheral resistance (TPR). Hydrochlorothiazide increased PRA, AII, and aldosterone, and lowered blood pressure mainly through a reduction in cardiac output. Enalapril was significantly more effective than hydrochlorothiazide in reversing structural changes in the retinal and hand vasculature as well as in the heart. A reduction in cardiac hypertrophy was seen even in the occasional enalapril-treated patient, in whom little or no reduction in blood pressure occurred. In the stepwise regression analyses, the changes in retinal and hand vascular structure were most strongly related to various changes in the RAAS, explaining 15 to 34% of the variance. For the changes in cardiac structure, the type of therapy (enalapril or hydrochlorothiazide) appeared to be the most important factor, explaining between 29 and 50% of the variance. The changes in cardiac structure were even more strongly related to changes in the RAAS for the enalapril treated patients and explained up to 55% of the variance in cardiac structure. It can be concluded that the reversal of structural vascular changes during antihypertensive therapy was more dependent on the blockade of the RAAS than on lowering of the blood pressure.
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PMID:Reversal of cardiovascular structural changes when treating essential hypertension. The importance of the renin-angiotensin-aldosterone system. 128 43

Enalapril, an angiotensin converting enzyme (ACE) inhibitor usually administered orally once daily, decreases blood pressure by lowering peripheral vascular resistance without increasing heart rate or output. It is effective in lowering blood pressure in all grades of essential and renovascular hypertension. Patients not responding adequately to enalapril monotherapy usually respond with the addition of a thiazide diuretic (or a calcium antagonist or beta-blocker), and rarely require a third antihypertensive agent. Enalapril is at least as effective as other established and newer ACE inhibitors, and members of other antihypertensive drug classes including diuretics, beta-blockers, calcium antagonists and alpha-blockers, but therapy with enalapril may be less frequently limited by serious adverse effects or treatment contraindications than with other drug classes. The most frequent adverse effect limiting all ACE inhibitor therapy in clinical practice is cough. This favourable profile of efficacy and tolerability, and the substantial weight of clinical experience, explain the increasing acceptance of enalapril as a major antihypertensive treatment and supports its use as logical first-line therapeutic option.
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PMID:Enalapril. A reappraisal of its pharmacology and therapeutic use in hypertension. 137 19

There is evidence that cardiac hypertrophy in spontaneously hypertensive rats (SHR) occurs before the development of hypertension. 1,2-Diacylglycerol, which is thought to be a second messenger activating protein kinase C, is also produced in excess in SHR hearts at 4 weeks of age, before established hypertension. We determined myocardial 1,2-diacylglycerol content in SHR with and without prazosin and enalapril from 3 to 4 weeks of age. Hearts from untreated SHR had greater RNA and DNA synthesis and greater relative weights at 4 weeks of age than those from Wistar-Kyoto (WKY) rats. There was no difference in triglyceride content or phospholipid species between WKY rats and untreated SHR, except for a higher cholesterol content in SHR. Treatment of SHR with enalapril, but not prazosin, lowered not only 1,2-diacylglycerol content but also RNA synthesis to the levels of WKY rats. Moreover, fatty acids involved in 1,2-diacylglycerol were altered by enalapril despite the lack of a difference between WKY rats and untreated SHR. Prazosin did not have any effect on 1,2-diacylglycerol fatty acid composition. Enalapril may decrease cardiac hypertrophy in SHR by lowering myocardial 1,2-diacylglycerol production.
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PMID:Enalapril reduces the enhanced 1,2-diacylglycerol content and RNA synthesis in spontaneously hypertensive rat hearts before established hypertension. 138 Oct 46

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
Hypertension 1992 Nov
PMID:Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. 142 16

Twenty five patients of mild to moderate uncomplicated essential hypertension and five with severe hypertension were treated with long acting converting enzyme inhibitor enalapril for six weeks. Diuretic was added in those patients who did not respond satisfactorily. Twenty one patients of mild to moderate hypertension had their diastolic blood pressure controlled at the end of the study; fifteen with enalapril alone and six with the help of diuretic. Remaining four showed a relative fall but not to level below 150/90 mm Hg. Only one patient with severe hypertension showed fall to normal levels. Four showed a relative fall but not to the normal level even with the addition of a diuretic. Enalapril is an effective anti hypertensive drug in mild to moderate essential hypertension.
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PMID:Enalapril in hypertension. 827 May 74

It is not clear whether regression of cardiac hypertrophy normalizes cardiac contractility. We studied the effect of enalapril treatment on the contractile response to beta-adrenergic stimulation with isoproterenol in renal hypertension. Male Wistar rats (n = 28) were divided into a clipped group (n = 14) and control group (n = 14). Three weeks after surgery, half of the animals from each group received for 21 days either enalapril (2.5 mg/kg) twice a day or vehicle by gastric intubation. Arterial pressure and body weight were measured twice a week. At the end of the experimental period, the hearts were excised, the ventricles were weighed, and the left ventricular papillary muscle was mounted in a bath. Myocardial contractility was characterized by the maximal developed tension, the maximal rate of rise of tension (+T), and the maximal velocity of relaxation (-T), which were measured at basal conditions and after cumulative doses of isoproterenol (10(-11) to 10(-4) M). The ratio of ventricular weight to body weight increased in hypertensive rats. Enalapril induced a decrease in arterial pressure and in the cardiac mass in both treated groups (p less than 0.05). The basal values of maximal developed tension, +T, and -T were similar in the four groups. The increment in +T and -T in response to isoproterenol (10(-4) M) was depressed in the hypertensive animals and in both treated groups (p less than 0.05). There was no significant difference in the +T/-T ratio or in the ED50 among the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Effect of enalapril on the inotropic response to isoproterenol in renal hypertensive rats. 153 Dec 7

We examined whether the renal protective effect of the angiotensin I converting enzyme inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP) is dose-related and associated with alterations in the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a stable breakdown product of prostacyclin. Enalapril maleate at 1.5, 5 and 15 mg/kg/day or vehicle was chronically administered to saline-drinking SHRSP (six per group) starting at 8.1 weeks of age. Vehicle-treated SHRSP developed severe hypertension, proteinuria and strokes (age at death, 14 +/- 1 weeks; mean +/- S.E.). Enalapril prolonged survival dose-dependently and reduced proteinuria; all SHRSP given 15 mg/kg/day lived beyond 23 weeks of age without evidence of stroke or proteinuria. There was no effect of enalapril at any dose on systolic arterial blood pressure in spite of variable levels of urinary protein excretion and onset of stroke in the different groups. Likewise, urinary 6-keto-PGF1 alpha and PGE2 excretion did not differ among the groups except for an increase in 6-keto-PGF1 alpha in the 15 mg/kg/day group at one week after initiation of enalapril therapy. These results are consistent with a dose-related renal protective action of enalapril in saline-drinking SHRSP that is not closely associated with sustained alterations in urinary excretion of renal vasodilatory PGs.
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PMID:The antiproteinuric action of enalapril in stroke-prone spontaneously hypertensive rats is unrelated to alterations in urinary prostaglandins. 154 1

This review compares the metabolism and pharmacokinetic profiles of captopril, the first orally active angiotensin-converting enzyme (ACE) inhibitor, and 2 newer ACE inhibitors, enalapril and quinapril. Captopril differs from both enalapril and quinapril in that its chemical structure contains a sulfhydryl group, the presence of which may be important in the development of adverse reactions. Captopril also differs from enalapril and quinapril in its ability to be metabolized in plasma. Enalapril and quinapril are both de-esterified, most likely in the liver, to their active metabolites, enalaprilat and quinaprilat. All 3 ACE inhibitors are eliminated primarily via renal excretion, and renal dysfunction markedly increases the area under the time versus plasma concentration curves. Hepatic dysfunction also slows the conversion of enalapril and quinapril to their active metabolites. There is evidence that both captopril and enalapril, but not quinapril, may accumulate with repeated dosing. The pharmacokinetics of these agents are not significantly modified by co-administration of other drugs. However, captopril does cause marked increases in trough plasma levels of digoxin. Overall, the pharmacokinetic profiles of captopril, enalapril, and quinapril make them suitable for a wide range of patients with hypertension or congestive heart failure.
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PMID:Comparative pharmacokinetics of captopril, enalapril, and quinapril. 154 41

Enalapril and trichlormethiazide were compared with respect to effects on the quality of life in a crossover study of 36 patients with hypertension. Multiple-choice 34-item questionnaires with three possible answers (severe, mild and none) per question were used to assess symptoms and mood. Twenty patients were initially given enalapril and 16 were initially given trichlormethiazide. There was no significant difference in the antihypertensive efficacy of the 2 drugs. Treatment with enalapril resulted in significant improvement in 11 of the 34 items, and a tendency for another 4 items to improve. Treatment with trichlormethiazide resulted in significant improvement in only 5 items and a tendency to improve in 2. When enalapril and trichlormethiazide were compared, significantly greater improvement in 2 items and a tendency toward greater improvement in 4 items was seen with enalapril treatment. Thus, enalapril was found to be more efficacious than trichlormethiazide with respect to quality of life in patients with hypertension.
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PMID:Crossover trial comparison of enalapril maleate and trichlormethiazide in the treatment of essential hypertension: emphasis on the quality of life. 160 Feb 61


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