Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 770 subjects enrolled into the French multicenter trial of Triatec (ramipril) presented the usual characteristics of moderate hypertension. After a low rate of response to placebo (9.1 p. 100), over half the active treatment patients responded to Triatec 2.5 mg (57 p. 100). Later on, Triatec 5 mg achieved control of half the remaining patients (55.6 p. 100); lastly, among non-responders to that posology, no difference was noted between monotherapy with 10 mg of Triatec, and the combination of 20 mg of Lasilix (furosemide) and Triatec 5 mg (respectively 44.7 p. 100 and 47.4 p. 10 responders). As a whole, more than 90 p. 100 of the patients responded to the proposed treatment plan.
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PMID:[Efficacy of Triatec in monotherapy and in combination with Lasilix in a French multicenter study]. 214 96

Angiotensin converting enzyme (ACE) inhibitors have offered new perspectives in the treatment of hypertension. The development of new ACE inhibitors such as ramipril provides an opportunity to improve the knowledge on this class of drug, and to optimize the benefit/risk ratio for the patient. Ramipril was selected among several analogs because of its unique physicochemical properties. It is a nonsulfhydryl ACE inhibitor, and after oral absorption it is transformed in the liver into its active metabolite ramiprilat, which is at least 23 times more lipophilic than enalaprilat. Furthermore, the in vitro affinity of ramiprilat for the enzyme is 7 times higher than for enalaprilat and 47 times higher than for captopril. The ramiprilat-ACE complex is therefore very stable and dissociates 6 times more slowly than the enalaprilat-ACE complex and 22 times more slowly than the captopril-ACE complex. Ramipril possesses a favorable pharmacokinetic profile as a consequence of its physicochemical properties: its high potency allows the use of very low doses, and the slow dissociation of the ramipril-ACE complex explains the long duration of its action, permitting a once-daily treatment. Dose-finding studies have confirmed that very low doses of ramipril--2.5 mg once a day--can be used as a first-step treatment of hypertension. This dose can be increased up to 5 mg, and if necessary a low dose of a diuretic can be added. Using this therapeutic scheme, ramipril normalized blood pressure, insuring that each patient receives the smallest effective dose. Inhibition of the tissue renin-angiotensin system by ramipril has been described in recent studies on animal models.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The renin-angiotensin system and ramipril, a new converting enzyme inhibitor. 248 29

Angiotensin-converting enzyme (ACE) has been identified as a prominent brush border membrane-bound enzyme of human jejunum. In this study, we purified brush border membrane vesicles enriched in ACE, and characterized the ACE with regard to (a) its stability in the membrane, (b) substrate hydrolysis kinetics compared with pulmonary endothelial ACE, and (c) pharmacologic interaction with Ramipril. These investigations resulted in the following findings. The uninhibited enzyme is stable in native membranes in vitro, with a half-life of 195 +/- 7 h. Kinetic analysis of ACE hydrolysis activity revealed the presence of a single enzyme species, which yielded a high Vmax and displayed a Km similar to purified ACE from lung endothelium. Brush border ACE was inhibited by Ramipril, one of the most specific and potent orally administered ACE inhibitors indicated for hypertension. We determined the brush border ACE value of IC50 = 3 X 10(-9) M Ramipril-diacid, which is the same value for serum and lung ACE. Brush border ACE remains 100% inhibited by 10 microM Ramipril during at least 8 days in vitro. The data indicate that ACE is a prominent jejunal brush border enzyme that behaves pharmacologically and kinetically like its peripheral circulation counterpart. This study suggests that high doses of orally administered ACE inhibitors may affect intestinal epithelial function.
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PMID:Human intestinal brush border angiotensin-converting enzyme activity and its inhibition by antihypertensive Ramipril. 283 Nov 5

Experimental uremia is known to cause cardiac hypertrophy. In the present study we examined the effect of uremia with or without concomitant treatment of hypertension by the converting enzyme Ramipril (125 micrograms/day) on micromorphometric indices of cardiac interstitium at the light microscopical and ultrastructural level. In male SD rats, 21 days of uremia caused an increase of total heart weight (1040 +/- 73 mg wet wt vs. 871 +/- 81 in controls, P less than 0.05) with an increase of both right and left ventricular weight. This was accompanied by reduction of capillary cross-sectional area despite unchanged capillary length. The volume density (cm3/cm3) of cardiomyocytes was unchanged (0.881 +/- 0.01 vs. 0.871 +/- 0.016 in controls), but volume density of interstitial tissue (excluding capillary lumen) was significantly increased (0.042 +/- 0.011 cm3 interstitial tissue/cm3 total heart tissue vs. 0.019 +/- 0.007 in controls). This was associated with signs of activation of interstitial cells, that is, increased volume of interstitial cell nuclei and interstitial cell cytoplasm. Concomitantly, a significant increase of volume density of non-cellular interstitial ground substance was found which was not normalized by antihypertensive treatment using Ramipril. After three months of uremia, electron microscopy showed collagen fiber deposition in the interstitium. Comparable interstitial fibrosis was not observed in hearts of rats with renovascular (one clip-two kidney) hypertension. It is concluded that uremia increases myocardial interstitial ground substance by mechanisms independent of hypertension. The data may be relevant for recent findings of diastolic heart malfunction secondary to impaired compliance in uremic patients.
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PMID:Myocardial interstitial fibrosis in experimental uremia--implications for cardiac compliance. 296 79

The converting enzyme inhibitor, ramipril, 20 mg once daily, was given to 3 hypertensive patients with unilateral renovascular disease. At 1 month, 24 hours after the last dose of ramipril, blood pressure, plasma angiotensin II and converting enzyme activity remained low, and active renin and angiotensin I high. There was no tendency for converting enzyme inhibition to be overcome during 1 month of ramipril therapy. Ramipril caused slight increases in serum potassium and urea, no change in serum creatinine and no consistent changes in the renal vein renin ratio. Ramipril caused little change in renal plasma flow on the stenotic side, but filtration fraction was reduced in 2 patients. There was no serious deterioration in total or individual glomerular filtration rate during ramipril therapy. The drug was well tolerated and there were no serious side effects. Ramipril, given once daily, is likely to be effective in controlling hypertension with renal artery stenosis.
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PMID:Ramipril for hypertension secondary to renal artery stenosis. Changes in blood pressure, the renin-angiotensin system and total and divided renal function. 303 22

Ramipril is a long-acting non-sulphydryl converting enzyme inhibitor that requires cleavage of its ester group to form the active diacid metabolite, ramiprilat. Renal excretion largely determines the drug's duration of action and the dosage should be reduced in patients with renal impairment. Oral ramipril given daily at dosages of 5 mg or more can control blood pressure over a 24-hour period; lower doses may be effective in patients with heart failure inadequately controlled by diuretics alone. No serious idiosyncratic adverse reactions have been reported. Ramipril is one of the most potent long-acting converting enzyme inhibitors developed; it is effective given once daily in the treatment of all grades of hypertension and of heart failure.
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PMID:Clinical pharmacology of ramipril. 303 28

Ramipril is a potent orally active converting enzyme inhibitor. Its active metabolite ramiprilat is classified as a reversible, slow- and tight-binding inhibitor. Ramipril lowers blood pressure in various models of hypertension and improves states of acute cardiac failure mainly by suppression of angiotensin II formation. Actions on both vasoconstrictor and volume factors are involved because ramipril causes vasodilation and mild natriuresis but preserves potassium. Sustained inhibition of converting enzyme in target tissues such as vascular wall, kidney and heart may explain cardiovascular changes over the long term. Ancillary effects may possibly emerge from modulation of the sympathetic nervous system but the contribution of bradykinin potentiation remains unclear.
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PMID:Ramipril: review of pharmacology. 303 30

We examined the effect of non-antihypertensive doses of the angiotensin-converting enzyme inhibitor ramipril, kinins, and/or nitric oxide on left ventricular hypertrophy in rats with aortic coarctation. We investigated the effect of either HOE 140, a specific B2 receptor antagonist, or NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the antihypertrophic effect of ramipril at non-antihypertensive doses (10 micrograms/kg per day) failed to alter left ventricular hypertrophy significantly, although a small decrease was obtained. Given at a dose of 1 mg/kg per day for 6 weeks, ramipril prevented increased blood pressure and left ventricular hypertrophy after aortic coarctation. Neither of these effects was blocked by simultaneous administration of HOE 140 (500 micrograms/kg per day). In rats with aortic coarctation treated with L-NAME, blood pressure increased further but left ventricular weight did not. Ramipril (1 mg/kg per day) significantly reduced left ventricular hypertrophy, although blood pressure was still higher than in rats given water alone. The slope of the correlation between left ventricular weight and blood pressure in rats that received L-NAME was significantly lower than in rats that did not (0.52 versus 1.29; P = .008). This suggests that for each 1 mm Hg that the blood pressure increased, the increase in left ventricular weight was less in the L-NAME groups. Thus, only antihypertensive doses of ramipril possessed antihypertrophic activity. Kinins did not participate in the chronic antihypertensive and antihypertrophic effects of ramipril. In hypertension induced or aggravated by chronic nitric oxide synthase, L-NAME partially impaired development of left ventricular hypertrophy for reasons that are unclear.
Hypertension 1994 Jun
PMID:Role of kinins and nitric oxide in the antihypertrophic effect of ramipril. 751 54

Ramipril is a second generation angiotensin converting enzyme (ACE) inhibitor. Like enalapril, it is a prodrug and is hydrolysed in vivo to release the active metabolite, ramiprilat, which has a long elimination half-life, permitting once-daily administration. The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies conducted in general practice as well as in more rigorously controlled clinical trials. In the former, approximately 85% of patients with mild to moderate essential hypertension have responded successfully to treatment with ramipril 2.5 or 5 mg/day, while comparative trials indicate that the antihypertensive efficacy of the drug is equivalent to that of other established ACE inhibitors and the beta-adrenoceptor antagonist atenolol. As expected, the response rate to ramipril monotherapy is lower in patients with severe hypertension (around 40%), although the blood pressure lowering effect can be enhanced with the addition of a diuretic such as hydrochlorothiazide or piretanide. The antihypertensive efficacy of ramipril is maintained in patients with diabetes mellitus and preliminary data indicate that the drug has the beneficial effect of decreasing urinary albumin excretion in diabetic patients with nephropathy. Ramipril is superior to atenolol in causing regression of left ventricular hypertrophy, although the clinical significance of this effect per se remains to be established. The large-scale Acute Infarction Ramipril Efficacy (AIRE) study demonstrated that ramipril 5 or 10 mg/day significantly decreased the risk of all-cause mortality by 27% in patients with clinical evidence of heart failure after acute myocardial infarction, even if transient. The beneficial effect of ramipril was apparent by 30 days of treatment and appeared to be greatest in patients with more severe ventricular damage after infarction. Ramipril is well tolerated in general practice, with 5% or fewer patients discontinuing therapy because of drug intolerance. The data available suggest that ramipril shares a similar tolerability profile to that of other established ACE inhibitors. Thus, clinical data confirm ramipril as a useful alternative ACE inhibitor for the treatment of patients with mild to moderate hypertension, and indicate a beneficial effect of the drug in patients with clinical evidence of heart failure after acute myocardial infarction. It is also reasonable to assume that ramipril will be of value in the treatment of patients with more established heart failure or asymptomatic left ventricular dysfunction.
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PMID:Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure. 777 15

Ramipril 5 mg once daily was compared to Captopril 50 mg twice daily in a randomised, double-blind, parallel group study in 60 patients with a diastolic blood pressure between 95 to 120 mmHg over a period of 2 months. Both drugs in the dose regimen used in this study exerted a similar anti-hypertensive effect at the end of 2 months of treatment resulting in a fall of supine diastolic blood pressure with Ramipril = 19.27 +/- 3.34 mmHg and Captopril = 19.15 +/- 2.63, in patients receiving the drugs without the diuretic. The mean fall in supine diastolic blood pressure 4 hours after the first dose of Ramipril was 6.5 mmHg and Captopril 8 mmHg. None of the patients developed first dose hypotension or orthostatic hypotension and there was no significant alteration of the heart rate in either group. The serum K+ levels remained unchanged in both groups of patients. Both drugs were well tolerated and there were no adverse effects observed on the liver, kidney, blood sugar or haemopoietic system. Based on the results of this study, it can be concluded that the antihypertensive efficacy of 5 mg ramipril in a once daily dose is equivalent to 50 mg captopril given twice daily. However an appreciably greater number of patients reported improvement in the "quality of life' parameters with ramipril as compared to captopril. Thus for the routine treatment of mild to moderate arterial hypertension, ramipril offers reliable antihypertensive efficacy in a once daily dose, thereby helping to improve patient compliance and making the treatment more economical.
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PMID:Ramipril vs captopril in mild to moderate hypertension. 786 Apr 71


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