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

The converting enzyme inhibitor, enalapril, was given to 20 hypertensive patients with renal artery stenosis in a single daily dose of 10-40 mg. Enalapril effectively controlled hypertension long-term, and only two of the 20 patients required concomitant diuretic treatment. The blood pressure reduction 6 h after the first dose of enalapril was significantly related to pre-treatment plasma concentrations of active renin and angiotensin II (AII), and to the concurrent fall in AII. Blood pressure fell further with continued treatment; the long-term reduction was not significantly related to pretreatment plasma renin or angiotensin II. At three months, 24 h after the last dose of enalapril, blood pressure, plasma AII and converting enzyme activity remained low, and active renin and angiotensin I (AI) high; 6 h after dosing, AII had, however, fallen further. During prolonged therapy, the increase of active renin was proportionately greater than that of angiotensin I. Enalapril alone caused a long-term reduction in exchangeable sodium, with slight increases in serum potassium, creatinine and urea. Enalapril alone did not impair overall renal function in five patients with bilateral renal lesions despite effective blood pressure reduction. Enalapril was well tolerated with no serious side-effects. Enalapril given once daily is effective in controlling hypertension associated with renal artery stenosis.
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PMID:Enalapril (MK421) in the treatment of hypertension with renal artery stenosis. 610 May 99

The mechanism of action of angiotensin converting enzyme (ACE) inhibitors to lower blood pressure remains unclear, but the weight of available data favour peripheral blockade of the formation of angiotensin II (AII). Previous work in rats has shown that the prodrug ACE inhibitor, enalapril (MK-421), lowered blood pressure most effectively when PRA was elevated [sodium deficiency, two-kidney, one figure 8 hypertension, diuretic-treated spontaneously hypertensive rats (SHR)]. In sodium-deficient rats, the enalapril-sensitive component of the blood pressure was greatly reduced after salt loading, and nephrectomy blocked the antihypertensive response to enalapril in SHR. In the present study, further support that the mechanism of action of enalapril involves a reduction in AII has been obtained from rats made hypertensive by continuous intravenous (i.v.) AII infusion for 10 days. Enalapril administered for seven days did not significantly lower blood pressure, suggesting that there were no important non-angiotensin mechanisms (such as bradykinin potentiation) involved in its action. From earlier studies in SHR, the time course for blockade of angiotensin I (AI) pressor responses and the blood pressure reduction did not correspond, suggesting a tissue site of action. In the present studies in adult SHR, a central site of action was ruled out since the parent inhibitor, enalaprilic acid (MK-422), injected into the brain ventricles did not acutely reduce blood pressure. An interaction of enalaprilic acid with the sympathetic nervous system was evaluated in dogs in which adrenergic activity was enhanced as a result of diuretic-induced renin release. Enlaprilic acid did not alter the enhanced hindquarter vasoconstrictor responses to sympathetic nerve stimulation. Enalapril increased renal blood flow, glomerular filtration rate and sodium excretion. The mechanism of the natriuresis in dogs probably involves several mechanisms including a decrease in aldosterone biosynthesis, changes in renal function (glomerular filtration rate and renal blood flow) and possibly blockade of a direct tubular effect of AII on sodium reabsorption. Enalaprlic acid was also studied in a closed chest dog model of acute left ventricular (LV) failure caused by embolization via the left main coronary artery with 50 microns plastic microspheres. Enalaprilic acid at 100 micrograms/kg i.v. reduced preload, afterload and improved LV performance without changing the heart rate. In conclusion, enalapril the prodrug, and enalaprilic acid the active inhibitor, are potentially useful in the treatment of hypertension and LV failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of action of enalapril in experimental hypertension and acute left ventricular failure. 610 Jun 9

Enalapril, a long-acting, non-sulfhydryl, angiotensin converting enzyme (ACE) inhibitor, is well absorbed after oral administration, and hydrolised to its bioactive form, enalaprilic acid (EA). Administration with food does not affect its bioavailability; elimination is predominantly renal. Peak serum EA concentrations occur 4 h after an oral dose; its serum half-life is approximately 35 h, and steady state is achieved by the fourth day of treatment. Enalapril controls blood pressure in essential and renovascular hypertension without affecting heart rate or cardiovascular reflexes. It also decreases serum concentrations of ACE (for greater than 24 h), angiotensin II and aldosterone, and increases plasma renin activity. Once and twice-daily regimens are equally effective. In patients with congestive heart failure refractory to digitalis and diuretics, enalapril increases cardiac output and decreases pulmonary capillary wedge pressure. Long-term treatment produces improvement in NYHA functional classification, exercise capacity and ejection fraction. Human experience to date indicates that enalapril is safe and well tolerated.
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PMID:The clinical pharmacology of enalapril. 610 Jun 10

When added to hydrochlorothiazide, enalapril is as effective as captopril in the treatment of moderate to severe hypertension. It is also effective when used as monotherapy, and may be incorporated into a regimen with diuretic and methyldopa or timolol for the treatment of more resistant patients. Enalapril has a good safety profile as measured by frequency of clinical and laboratory adverse experiences.
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PMID:The efficacy and safety of enalapril in moderate to severe essential hypertension. 610 Aug 71

To date, more than 5000 patients have had experience with enalapril. Over 1000 subjects have been exposed to the drug for more than one year and approximately 600 for over two years. In controlled trials, 2249 subjects, who included normal volunteers and patients with hypertension and congestive heart failure, have received enalapril alone or concomitantly with hydrochlorothiazide or other antihypertensive agents. There have been no deaths attributed to enalapril. The incidence of serious adverse experiences in controlled trials was similar to placebo, and was not higher in the elderly. The incidence of adverse experiences was not dose-related. Drug discontinuation due to adverse experiences was 3.5%, similar to placebo, and approximately half that of control drugs. Serious laboratory adverse experiences were rare. Enalapril attenuated the adverse metabolic effects of hydrochlorothiazide, particularly hypokalaemia. Skin rash occurred in approximately 1.0% of patients. One case of transient taste loss occurred on enalapril, and one on enalapril in combination with hydrochlorothiazide. Neutropenia and agranulocytosis were not encountered. Mean white blood cell counts did not change overall. Most patients (approximately equal to 80%) show no change or an improvement in renal function on enalapril. Discontinuation of concomitant hydrochlorothiazide usually normalized renal function. Enalapril is well tolerated in renal insufficiency. Azotaemia may occur in bilateral renovascular hypertension. Proteinuria was rarely seen and often improved on enalapril. Compassionate use protocols have been available to patients either resistant or intolerant to captopril. Of 68 patients admitted for captopril-related skin rashes, only five recurred on enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Overall tolerance and safety of enalapril. 610 Aug 72

Enalapril alone, 10-40 mg given once-daily, controlled systemic hypertension long-term (mean follow-up time 19 months) in patients with renal artery stenosis. Significant, but usually modest, increases in serum creatinine and urea were observed. No serious side-effects were seen. A highly significant reduction in peripheral plasma angiotensin II was maintained 24 h after the previous dose of enalapril. Plasma active renin concentration rose 20-fold with long-term enalapril, when the stenotic kidney showed significant secretion of inactive, as well as of active renin. With enalapril therapy, the contralateral kidney showed net extraction of active renin. In unilateral renal artery stenosis, circulation on the affected side is diminished and is mainly via the juxtamedullary nephrons, which become rich in associated renin. Important intrarenal compensatory actions of the renin-angiotensin system include support of glomerular filtration, enhancement of vasa recta-mediated counter-current exchange, sustained urea excretion and maintenance of renal artery pressure distal to the stenosis. These compensatory effects are lost with converting enzyme inhibition. Thus in patients who are candidates for operation, enalapril should usually be given for no more than one month before proceeding to corrective surgery, to allow maximum blood pressure reduction without endangering the stenotic kidney for too long. Enalapril can nevertheless be given effectively long-term in patients unsuitable for corrective surgery.
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PMID:Enalapril in hypertension with renal artery stenosis: long-term follow-up and effects on renal function. 610 Aug 83

Enalapril maleate is an investigational oral prodrug whose hydrolyzed diacid metabolite is a potent angiotensin-converting enzyme inhibitor. Fourteen patients with mild to moderate hypertension were evaluated after receiving placebo, and two weeks of treatment with each of the following: enalapril maleate (20 mg b.i.d.), hydrochlorothiazide (25 mg b.i.d.), and the two in combination. In comparison to placebo, the magnitudes of the blood pressure reduction after enalapril and hydrochlorothiazide alone were comparable. The reduction in blood pressure following enalapril was evident throughout the 12-hour dosing interval. The combination of enalapril and hydrochlorothiazide resulted in a marked further reduction in blood pressure that was greater than that predicted from the responses to the individual drugs (P less than 0.05). Biochemical parameters confirmed inhibition of angiotensin-converting enzyme during enalapril treatment; serum angiotensin-converting enzyme activity proved an excellent monitor of compliance. Enalapril was generally well tolerated. Adverse effects included symptomatic hypotension in three patients when enalapril was first added to hydrochlorothiazide and hyperesthesia of the oral mucosa without a loss of taste in one patient on enalapril. Enalapril maleate alone and especially in combination with hydrochlorothiazide appears to be an effective, well-tolerated converting enzyme inhibitor with at least a 12-hour duration of action.
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PMID:Comparative antihypertensive effects of enalapril maleate and hydrochlorothiazide, alone and in combination. 630 68

The converting enzyme inhibitor enalapril, in single daily doses of 10-40 mg, was given to 20 hypertensive patients with renal artery stenosis. The blood pressure fall six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II and to the concurrent fall in angiotensin II. Blood pressure fell further with continued treatment; the long term fall was not significantly related to pretreatment plasma renin or angiotensin II concentrations. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, fallen further. The rise in active renin during long term treatment was proportionally greater than the rise in angiotensin I; this probably reflects the fall in renin substrate that occurs with converting enzyme inhibition. Enalapril alone caused reduction in exchangeable sodium, with distinct increases in serum potassium, creatinine, and urea. Enalapril was well tolerated and controlled hypertension effectively long term; only two of the 20 patients required concomitant diuretic treatment.
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PMID:Enalapril in the treatment of hypertension with renal artery stenosis. 631 26

In this case we are reporting on a patient suffering from malignant renovascular hypertension and chronic renal failure due to occlusion of both renal arteries. The acute renal insufficiency after Captopril and later on after Enalapril treatment was fully reversible. We believe that the acute reversible renal insufficiency was caused by the blockage of glomerular autoregulation depending on Angiotensin II.
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PMID:[Reproducibility of acute captopril-induced renal insufficiency with enalapril]. 632 50

Angiotensin-converting enzyme (ACE) inhibitors favorably modify control mechanisms that are disturbed in hypertension and congestive heart failure, principally, but perhaps not exclusively, through reduction in angiotensin II levels. Pharmacodynamic actions are vasodilation, increased sodium excretion, and lowering of blood pressure. Investigations with captopril and enalapril in the treatment of hypertension indicate efficacies comparable to each other and to current step 1 and 2 agents. Enalapril is more potent than captopril and has a longer duration of action. The hemodynamic mechanism of action is reduction in peripheral vascular resistance. Addition of a diuretic potentiates blood pressure lowering and proportion of patients responding. When used in congestive heart failure, ACE inhibitors exert a balanced vasodilator effect on arterial and venous beds and do not induce tachycardia or fluid retention. Cardiac output is increased whereas systemic vascular resistance, central pressures, and systemic blood pressure are reduced acutely and chronically. Although captopril is associated with certain side effects, possibly resulting from the sulfhydryl group in its structure, this profile has not been encountered thus far in clinical investigations with enalapril. The effects of ACE inhibitors on the natural histories of hypertension (independent of blood pressure lowering) and congestive heart failure are yet to be determined.
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PMID:Overview: the role of angiotensin-converting enzyme inhibitors in cardiovascular therapy. 632 21


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