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

Perindopril is a long acting angiotensin-converting enzyme inhibitor with a perhydroindole group and no sulphydryl radical. Perindopril is a pro-drug that is hydrolyzed to the active metabolite perindoprilat. Perindopril is rapidly absorbed, reaching peak plasma concentrations about 1 h after a single oral dose. Its bioavailability is greater than 70% and is not influenced by meals. Perindoprilat reaches peak plasma concentrations 3 to 4 h after administration. The blood pressure lowering effect of perindopril has been shown in animal models with spontaneous and renovascular hypertension. In hypertensive patients dose response studies have shown a significant and linear relationship between the dose and the activity of perindopril. The antihypertensive efficacy of 4 and 8 mg doses is significantly greater than that of 2 mg or of placebo. The maximal response is attained about 4 to 6 h after the first dose. As demonstrated by 24 h blood pressure recordings in ambulatory patients, the antihypertensive activity of perindopril was still significant 24 h after the last dose. Clinical trials have indicated that perindopril is at least as effective as usual therapeutic doses of captopril, atenolol or a combination of hydrochlorothiazide plus amiloride in mild to moderate essential hypertension. Oral administration of 4 to 8 mg od significantly reduced supine and standing systolic and diastolic blood pressure, and adequate diastolic blood pressure control was attained in about 60 to 70% of patients with monotherapy. In the majority of patients, hypertension was controlled with a daily dose of 4 mg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical review of perindopril in the treatment of hypertension. 795 37

We examined the dose-related effects of angiotensin-converting enzyme inhibitors on circulating and tissue levels of angiotensin and bradykinin peptides by administering perindopril or lisinopril to rats in drinking water for 7 days. A reduction in the ratio of plasma angiotensin II (Ang II) to Ang I was seen for 0.006 mg/kg per day perindopril, with an increase in plasma renin and Ang I at 0.017 mg/kg per day. Plasma Ang II levels did not decrease until 1.4 mg/kg per day perindopril, at which dose plasma Ang I levels reached a plateau of an approximate 25-fold increase. The effects of perindopril on Ang II and Ang I levels in heart, lung, aorta, and brown adipose tissue were parallel to those observed for plasma. By contrast, renal Ang I levels did not increase, and renal Ang II levels decreased by 40% at 0.017 mg/kg per day, the same threshold seen for the increase in plasma renin. Perindopril increased circulating bradykinin-(1-9) levels approximately eightfold, with a threshold dose of 0.052 mg/kg per day, and increased bradykinin-(1-9) levels in kidney, heart, and lung in parallel with the changes observed for plasma. By contrast, aortic and brown adipose tissue bradykinin-(1-9) and bradykinin-(1-7) levels increased severalfold for perindopril doses as low as 0.006 mg/kg per day. Lisinopril also increased aortic bradykinin-(1-9) and bradykinin-(1-7) levels at doses below the threshold for the decrease in the ratio of Ang II to Ang I. These data indicate that renal Ang II levels and vascular bradykinin-(1-9) levels respond to low doses of converting enzyme inhibitor and may be important mediators of the effects of these compounds. The parallel increases in bradykinin-(1-9) and bradykinin-(1-7) levels in aorta and brown adipose tissue, at inhibitor doses below the threshold for inhibition of Ang I conversion, may result from a mechanism different from inhibition of "classic" angiotensin-converting enzyme.
Hypertension 1994 Apr
PMID:Effects of converting enzyme inhibitors on angiotensin and bradykinin peptides. 814 13

Angiotensin-converting enzyme (ACE) inhibitors are well established antihypertensives. Their effect on kidney function, however, seems to depend on the pathophysiological mechanisms underlying the clinical symptoms. In one part of the Perindopril and Therapeutic Safety Study (PUTS) the effect of a 6-week treatment with placebo or 4 mg/d of perindopril (Coversum, CAS 82834-16-0) on kidney function and albuminuria was investigated in 56 hypertensives with concomitant nephropathy. The study was performed as multicenter, randomized, placebo-controlled, double-blind study. The results show that perindopril reduced blood pressure effectively. The responder rate determined as a fall in blood pressure at least about 10 mmHg in the perindopril group was 39% vs. 21% in the placebo group. All investigated parameters of kidney function like serum creatinine, creatinine clearance, urinary excretion of albumin and alpha 1-microglobulin remained unchanged during the study. In a subgroup of patients with isolated albuminuria ACE inhibition reduced significantly the urinary albumin excretion (perindopril: -292 +/- 205 mg/g creat. vs. placebo: +61 +/- 48 mg/g creat: p < 0.05). From this study it can be concluded that in hypertension with concomitant nephropathy, except renovascular hypertension and hypertension in renal transplant recipients, ACE inhibition by perindopril will not impair kidney function. In the early phase of nephropathy with isolated albuminuria and normal serum creatinine perindopril improves albuminuria and seems to be even of benefit for the kidney.
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PMID:Therapeutic safety of perindopril in the treatment of mild hypertension with concomitant nephropathy. 821 41

The antihypertensive efficacy and acceptability of perindopril, an angiotensin-converting enzyme (ACE) inhibitor, was evaluated in 2,927 elderly (> or = 70 years) hypertensive patients in general practice, as part of an open 6-month trial conducted on a total of 23,460 patients with mild-to-moderate hypertension. Patients were ambulatory and selected if diastolic blood pressure (DBP) was between 94 and 115 mm Hg and no serious illness or ACE inhibitor intolerance was known. Perindopril was started at 2 or 4 mg once daily and, if supine DBP remained > 90 mm Hg, the daily dose could be doubled after 1 or 3 months (or a diuretic added if perindopril titration reached 8 mg). At entry, the 2,927 patients (65% females) were on average 74 years old, body weight was 68.2 kg, duration of hypertension was 9.4 years, and prior antihypertensive treatment was present in 78%. Percentage of normal DBP (< or = 90 mm Hg) was 69% at 1 month, 86% at 3 months (in patients on perindopril alone), and 94% at 6 months. At 6 months the reduction of systolic blood pressure and DBP was 28 and 16.6 mm Hg, respectively. Of the 2,927 patients at entry, 8.6% dropped out during the trial, including 6.1% due to side effects. Cough was the most common symptom (8.9%) leading to withdrawal in 3.4% of cases. In one patient, serum creatinine increased (3-fold at 1 month), but overall no significant variation of renal function occurred, as shown by stable plasma creatinine and potassium levels.
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PMID:Antihypertensive efficacy and acceptability of perindopril in elderly hypertensive patients. 832 64

A multicenter, double-blind, randomized, and placebo-controlled trial, the Perindopril Therapeutic Safety Study (PUTS), was designed to assess the interaction between angiotensin-converting enzyme (ACE) inhibition and the diseases and therapies commonly found associated with mild hypertension. A total of 480 male and female patients aged 30-70 years with a diastolic pressure of 90-104 mm Hg were included after a 3-week placebo run-in if they satisfied standard criteria for any of the following: hyperlipidemia, type II diabetes, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive lung disease or treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). At the end of the placebo run-in period, patients were randomly assigned to either placebo or perindopril 4 mg once daily. A total of 460 patients completed the 6-week double-blind phase, comprising 3 assessments at 1, 3, and 6 weeks. In this report, the principal results obtained in 5 disease groups (hyperlipidemia, type II diabetes, ischemic heart disease, nephropathy with proteinuria, and NSAID treatment) will be reported. A total of 269 patients belonging to one of the aforementioned 5 disease groups completed the double-blind phase of the study and were included for statistical evaluation. In the perindopril group, systolic and diastolic blood pressures decreased significantly more than in the placebo group, and a sitting diastolic blood pressure of 90 mm Hg was achieved in 65% of patients in the perindopril group and 30% of patients in the placebo group. The incidence of symptoms spontaneously reported by the patients was low: 2 patients of the perindopril group complained of cough.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new trial of the efficacy, tolerability, and safety of angiotensin-converting enzyme inhibition in mild systemic hypertension with concomitant diseases and therapies. Perindopril Therapeutic Safety Study Group (PUTS). 832 65

Angiotensin II (Ang II) may cause cardiovascular hypertrophy as a consequence of increased blood pressure or possibly by direct trophic actions. To dissociate Ang II and blood pressure in young spontaneously hypertensive rats (SHR), we used sodium loading during angiotensin converting enzyme inhibitor treatment. Animals were treated between 6 and 10 weeks of age with perindopril to lower Ang II and blood pressure, or with perindopril and 1% saline drinking fluid or perindopril and aldosterone infusion to lower Ang II but maintain high blood pressure. Blood pressure, heart weight, and media/lumen ratio of mesenteric resistance arteries were studied while rats were on treatment at 10 weeks of age and 15 weeks after treatment at 25 weeks of age. Perindopril lowered blood pressure and inhibited the development of cardiovascular hypertrophy. Saline or aldosterone restored high blood pressure during perindopril treatment and resulted in increased heart weight/body weight and resistance artery media/lumen ratios in direct proportion to the elevation of blood pressure. Because increased structure occurred despite perindopril treatment, we conclude that direct trophic actions of Ang II are not essential for the development of cardiovascular hypertrophy in young SHR and that the antitrophic actions of angiotensin converting enzyme inhibitors depend more on changes in blood pressure than on Ang II. However, restoration of blood pressure and structure by sodium during perindopril treatment raises the possibility that the design of the cardiovascular system and blood pressure may depend indirectly on Ang II through effects on sodium metabolism.
Hypertension 1993 Jan
PMID:Angiotensin II, sodium, and cardiovascular hypertrophy in spontaneously hypertensive rats. 841 23

Efficacy and acceptability of perindopril (Coversyl) in general practice were evaluated in 23,460 hypertensive patients (52.9% women) during an open six month trial. Patients had essential mild to moderate hypertension (94 mmHg < supine DBP < 115 mmHg) associated or not with obesity (34%), diabetes (12%), hypercholesterolemia (36%), smoking habits (24%). Mean hypertension duration was 6.5 years, 70 p. cent of patients were 50 to 69 years old and 12 p. cent 70 years old or more. Perindopril was started at 4 mg except in older and patients with renal insufficiency (2 mg). If supine DBP remained > 90 mmHg the dose was doubled up to 8 mg/day, then a thiazide diuretic was added. Monotherapy was held in 90 p. cent of cases all along the study, more than 8 over 10 times at 2 or 4 mg/day. Normalized patients (DBP < or = 90 mmHg) were 69.87 and 95 p. cent respectively at the first, third and sixth month. Mean supine SBP and DBP decrease were 27.3 and 18.0 mmHg. Antihypertensive activity was similar in patients taking psychotrope or non steroidal anti-inflammatory agents and in others, as well as in older (> or = 70 years), diabetics and obeses, however with a significantly more frequent bitherapy in these last three sub-groups. Cough, a well known side effect of ACEI led to withdrawal in only 2.6 p. cent of cases. Withdrawals for side-effect were more frequent in older patients (6.1%), in those taking psychotrope (5.3%) or non steroidal anti-inflammatory agents (6.0%) than in diabetics (4.1%) or the others (4.1%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Antihypertensive action, clinical and biological acceptability of perindopril: main results in 23,460 patients with mild to moderate hypertension treated for 6 months in general practice]. 848 Sep 86

To assess the role of the renin-angiotensin system (RAS) in the renal alterations of the lyon hypertensive (LH) rat, the renal function of LH rats and of their normotensive (LN) controls was studied at different pressure levels after an early and chronic blockade of the RAS by perindopril (3 mg.kg-1.day-1 orally from 3 to 15 wk of age) and after an acute infusion of angiotensin II (ANG II, 10 or 50 ng.kg-1.min-1). Over the range of renal perfusion pressures studied (115-165 mmHg), control LH differed from LN rats by an increased preglomerular vasoconstriction and a blunted pressure-natriuresis curve. Perindopril fully prevented the development of hypertension in LH rats, suppressed their preglomerular vasoconstriction, and markedly improved their pressure-natriuresis. In perindopril-treated LH, ANG II produced a greater reduction in renal blood flow, glomerular filtration rate, and urinary sodium excretion that was not significantly modified by blockade of thromboxane A2-prostaglandin H2 receptors. These results indicate that the blood pressure level and the renal function of LH rats are closely dependent on an active RAS.
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PMID:In the Lyon hypertensive rat, renal function alterations are angiotensin II dependent. 877 Jan 33

Angiotensin-converting enzyme inhibitors reduce blood pressure and cardiac mass but may also have a direct effect on myocardial growth. To test this hypothesis, we studied the effects of perindopril on the weight of transplanted hearts in which the left ventricle does not pump blood. Hearts were transplanted between littermate 10-week-old male spontaneously hypertensive rats, and recipients were treated for 2 weeks with vehicle (n = 10), perindopril (3 mg/kg per day) (n = 9), perindopril (3 mg/kg per day) plus the selective bradykinin B2 receptor antagonist Hoe 140 (500 micrograms/kg per day) (n = 13), or angiotensin II (200 ng/kg per minute) (n = 12). Perindopril reduced blood pressure and native left ventricular weight and also caused a significant decrease in the weight of the transplanted left ventricle compared with controls. Hoe 140 did not significantly alter blood pressure or native left ventricular weight of perindopril-treated rats but caused a significant increase in the weight of the transplanted left ventricle compared with rats treated with perindopril alone. Angiotensin treatment resulted in a significant increase in blood pressure and native left ventricular weight but no significant change in the weight of the transplanted left ventricle. Blood pressure and left ventricular weight for native but not for transplanted hearts were positively correlated. Therefore, in the absence of mechanical load, the weight of the left ventricle of spontaneously hypertensive rats responds little to angiotensin II but can be reduced by angiotensin-converting enzyme inhibition. The effect of perindopril on transplanted hearts of spontaneously hypertensive rats appears to depend on bradykinin.
Hypertension 1996 Oct
PMID:Cardiac transplantation, perindopril, and left ventricular hypertrophy in spontaneously hypertensive rats. 884 88

The transgenic rat TGR(mRen-2)27 develops severe hypertension with high adrenal renin and low kidney renin. The mechanism of suppressed kidney renin in these animals is still unclear. We investigated the effect of the angiotensin converting enzyme (ACE) inhibitor, perindopril on the renin-angiotensin system in plasma and tissues (adrenal gland and kidney), and the effect of mouse renin antibody on plasma and tissue renin activity before and after perindopril administration. Perindopril lowered blood pressure in the TGR(mRen-2)27 rats from 254.5 +/- 7.4 mm Hg to 154 +/- 7.8 mm hg (n = 8, P < .0001), while blood pressure in the untreated TGR (mRen-2)27 rats increased from 253.7 +/- 8.1 to 276.1 +/- 14.3 mm Hg during the study period. Perindopril significantly suppressed plasma angiotensin II (Ang II) from 19.4 +/- 2.5 pg/mL to 2.6 +/- 0.4 pg/mL, P < .0001, while markedly increasing plasma renin concentration (PRC) from 15.5 +/- 1.8 ng AngI/mL/h to 148.2 +/- 35.5 ng AngI/mL/h, P < .005 and kidney renin from 56.7 +/- 18.1 micrograms AngI/g/h to 827.4 +/- 79.1 micrograms AngI/g/h, P < .0001. However, adrenal renin was not increased. A mouse Ren-2 renin antibody at a 1:1000 dilution that suppresses purified mouse Ren-2 renin activity by 62.6 +/- 3.6% (n = 3, P < .0001) and does not suppress renin activity in plasma and kidney of the Sprague-Dawley rats, suppressed PRC in the untreated TGR(mRen-2)27 rats by 52.3 +/- 3.5% (n = 6, P < .0001). However, it only suppressed PRC in the perindopril treated TGR(mRen-2)27 rats by 7.0 +/- 2.4% (n = 6, P < .05). The antibody suppressed adrenal renin in both untreated and perindopril treated TGR(mREN-2)27 rats by 57.3 +/- 5.4% (n = 5, P < .0001) and 49.7 +/- 2.2% (n = 6, P < .0001), respectively. On the other hand, the mouse antibody suppressed kidney renin in the untreated TGR(mRen-2)27 rats by only 11.0 +/- 3.3% (n = 6, P < .05), and did not suppress kidney renin in the perindopril treated TGR(mRen-2)27 rats (n = 6, P < .0001), respectively. On the other hand, the mouse antibody suppressed kidney renin in the untreated TGR(mRen-2)27 rats by only 11.0 +/- 3.3% (n = 6, P < .05), and did not suppress kidney renin in the perindopril treated TGR(mRen-2)27 rats (n = 6, P < NS). The pH profile of renin activity in plasma confirmed the results of the antibody study. We conclude that in the TGR(mRen-2)27 rats adrenal renin is mainly mouse renin and kidney renin is mainly rat renin. The main sources of circulating renin in the TGR(mRen-2)27 rats are extra-renal tissues, including the adrenal glands, where mouse Ren-2 renin transcripts are highly expressed. The increased circulating renin in perindopril treated TGR(mRen-2)27 rats is rat renin derived from the kidney. The failure of adrenal renin to increase with perindopril suggests that at least in the basal state there is no feedback inhibition as there is in the kidney. The low kidney renin appears to be due to physiological rather than genetic factors.
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PMID:Reversal of the suppressed kidney renin level in the hypertensive transgenic rat TGR(mRen-2)27 by angiotensin converting enzyme inhibition. 884 72


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