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

1. Arterial remodelling is an important mechanism in the pathophysiology of hypertension and its complications, being involved in the decrease of vascular reserve, the autoregulation of cerebral blood flow and the development of atherosclerosis. There is now evidence that, in addition to several other growth factors, vasoactive peptides such as angiotensin II may act as vascular smooth muscle growth-promoting substances. Based on these data, the effects of perindopril, a potent and long-lasting angiotensin-converting enzyme (ACE) inhibitor, on structural and mechanical properties of the arterial wall have been studied in animal models of hypertension. Perindopril completely reversed the aortic medial hypertrophy and arterial stiffening observed in renovascular hypertensive rats and in spontaneously hypertensive rats. The effect of perindopril was consistent with the potent inhibition of vascular ACE, and emphasized the potential role of angiotensin II as a vascular growth modulator. Whether the time constant of remodelling is similar or not in the heart and large vessels remains an important question that requires further investigation.
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PMID:Remodelling of the vascular system in response to hypertension and drug therapy. 139 15

1. Perindopril's effectiveness in mild to moderate hypertension was evaluated in three studies. 2. Perindopril was more effective than sodium restriction in reducing blood pressure, and the effects were additive. 3. Perindopril was as effective as atenolol in reducing blood pressure, and was well tolerated. 4. Perindopril lowered blood pressure to the same extent as enalapril at peak drug levels but had a greater effect at the trough level of the drugs. 5. Perindopril is an effective antihypertensive agent with an acceptable side-effect profile in people with hypertension.
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PMID:Clinical efficacy of perindopril in hypertension. 139 18

Despite a marked reduction in cardiovascular morbidity and mortality, treated hypertensive patients remain at increased risk of coronary artery disease and its complications compared with untreated normotensive subjects. Mild hypertension is often associated with other, usually chronic, diseases. The failure of first-line antihypertensive therapy to deal adequately with concomitant disease and associated therapy might account for the poor improvement in the cardiovascular prognosis. This possibility has been addressed in an ongoing trial of novel design, the Perindopril Therapeutic Safety Study, a multicenter, double-blind, randomized and placebo-controlled trial to determine the safety, efficacy, and interaction of angiotensin-converting enzyme (ACE) inhibition with eight of the most common concomitant diseases and their therapies. A total of 480 male and female patients (60 per disease group) 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 disease, nephropathy with proteinuria, chronic obstructive lung disease, or rheumatoid arthritis. Of these, 460 patients have completed the 6-week double-blind phase (comprising two assessments, at 3 and 6 weeks), and are currently undergoing assessments every 3 months over a 1-year follow-up period. The end points include the incidence of progression or improvement in concomitant disease, the incidence of positive or negative interaction between ACE inhibition and concomitant therapy, change in blood pressure, adverse biochemical and hemodynamic reactions, self-reported side effects, and quality of life indices. Interim results for the 6-week double blind phase will shortly be available. However, the desirability and feasibility of conducting a study according to this novel design have already been proved.
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PMID:Angiotensin-converting enzyme inhibition in mild hypertension with concomitant diseases and therapies: an efficacy, safety, and compatibility study of novel design, the Perindopril Therapeutic Safety Study. 158 Feb 90

Perindopril is a long acting angiotensin converting enzyme (ACE) inhibitor, which displays similar pharmacodynamic properties to other agents in this class. In common with enalapril, it is also a prodrug. After absorption, perindopril is hydrolysed to the active metabolite, perindoprilat, and with once daily administration adequate 24-hour inhibition of ACE is obtained. Perindopril 4 to 8mg once daily is usually effective for blood pressure control in patients with mild to moderate essential hypertension. Those patients who do not respond adequately to monotherapy with perindopril usually respond with the addition of a second agent, such as a thiazide diuretic. General practice trials indicate that perindopril is at least as effective and as well tolerated as usual therapeutic dosages of captopril, atenolol or hydrochlorothiazide plus amiloride in mild to moderate essential hypertension. Preliminary results indicate that perindopril may also be effective in patients with severe hypertension or congestive heart failure. Perindopril is generally well tolerated and has an adverse effect profile similar to that of other ACE inhibitors. It further clinical experience confirms initial findings, perindopril is likely to represent a useful alternative to other members of the ACE inhibitor class in all grades of hypertension and congestive heart failure.
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PMID:Perindopril. A review of its pharmacological properties and therapeutic use in cardiovascular disorders. 171 88

Vascular remodeling is central to the pathophysiology of hypertension and atherosclerosis. The effects of antihypertensive drugs on this process are important to consider from a mechanistic and a pathogenetic point of view in relation to vascular complications of hypertension, e.g., decrease in vascular reserves, shift in cerebral blood flow autoregulation and atherosclerosis development. There is now evidence that, in addition to several other growth factors, vasoactive peptides such as angiotensin II may act as vascular smooth muscle growth promoting substances. Based on these data, the effects of perindopril, a potent and long-lasting angiotensin-converting enzyme (ACE) inhibitor, on structural and mechanical properties of the arterial wall, have been studied in animal models of hypertension as well as in humans. Perindopril completely reversed aortic medial hypertrophy and arterial stiffening observed in renovascular hypertensive rats. Similar benefits were reported in mesenteric resistance vessels of spontaneously hypertensive rats. The effect of perindopril was totally in keeping with potent inhibition of vascular ACE and emphasized the potential role of angiotensin II as a vascular growth modulator. Clinical studies confirmed animal experiments; both suggest that increases in arterial compliance and distensibility following perindopril is likely to be related to drug-induced modification of the arterial wall, at least partially independently of blood pressure reduction. The increase in arterial compliance was associated with a selective decrease in pulse pressure, a finding that is important, not only for the arterial wall, but also for the structure and function of the hypertensive heart.
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PMID:Vascular effects of perindopril: from experimental to clinical investigation. 172 97

Thirty-six hypertensive patients with impaired renal function entered a long-term study to assess the safety of perindopril. There were 28 men and 8 women of mean age 57.1 +/- 2.0 years (mean +/- SEM). The duration of documented hypertension was 7.3 +/- 1.2 years. Perindopril was given orally in single daily doses. The initial dosage was chosen according to the degree of renal function impairment: 29 patients received 4 mg o.d. [creatinine clearance (Clcr), 42.2 +/- 3.2 ml.min-1] and 7 patients received 2 mg o.d. (Clcr, 22.3 +/- 3.1 ml.min-1). Patients in whom blood pressure was not controlled had their dose doubled and then, if necessary, an additional diuretic therapy was added at subsequent visits. Six patients were withdrawn for adverse events (myocardial infarction, pneumonia, leucopenia in a patient who had lupus, diabetes mellitus, skin rash, epigastric pain), two patients were withdrawn for poor compliance, and three for personal convenience. The mean duration of treatment was 10.2 months with a range of 3-12 months (excluding one patient who died from myocardial infarction in the first days of the study and was not included in the analysis). Systolic and diastolic blood pressure decreased significantly (from 170.5/100.6 +/- 3.4/1.8 mm Hg to 151.8/88.8 +/- 3.0/1.7 mm Hg, n = 35, p less than 0.001). Baseline and final values of plasma creatinine (from 223.7 +/- 22.7 to 234.7 +/- 28.5 mumols/l), Clcr (42.5 +/- 3.2 to 45.7 +/- 4.6 ml.min-1), and kalemia (from 4.4 +/- 0.1 to 4.7 +/- 0.1 mmol/L) were not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term tolerance of perindopril in hypertensive patients with impaired renal function. 172 1

During the development of hypertension in young spontaneously hypertensive rats (SHR) vascular resistance is increased, particularly in the renal circulation, and, to a lesser extent, in the splanchnic bed. Treatment with angiotensin converting enzyme inhibitors in young SHR reverses the renovascular abnormalities more effectively than simple vasodilators, suggesting that the resistance changes may depend on angiotensin II. Perindopril treatment during the development of hypertension causes a reduction in blood pressure as a result of a fall in total peripheral resistance, which persists long after treatment is stopped. These long-term effects can be prevented by replacing angiotensin during perindopril treatment. Not all organs share the long-term resistance changes following perindopril treatment, which are most marked in the renal, splanchnic, and cerebral circulations. The heterogeneous patterns of regional vascular resistance during the development and after prevention of hypertension with angiotensin converting enzyme inhibitors in SHR suggest that local factors, for example, angiotensin II related to the tissue renin-angiotensin system or local adrenergic activity, may be important in the genesis of high blood pressure in this genetic model.
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PMID:Angiotensin converting enzyme inhibitors, regional vascular hemodynamics, and the development and prevention of experimental genetic hypertension. 204 11

The effects of specific active immunization against renin were compared with those of chronic angiotensin converting enzyme (ACE) inhibition. Male spontaneously hypertensive rats (SHR) were immunized (SHR-I) (n = 10) against pure murine renin (four injections of 30 micrograms/kg s.c.) or received (SHR-P) (n = 11) a converting enzyme inhibitor (perindopril, 2 mg/kg/day per os for 4 weeks). Sham-immunized SHR (SHR-S) (n = 12) and normotensive Wistar-Kyoto (WKY-S) (n = 12) rats served as controls. At 15 weeks of age, 24-hour average blood pressure was obtained in freely moving rats using intra-aortic pressure recording with computer analysis. Antirenin immunization induced high circulating titers of antibodies, a fall in plasma renin activity (-95%), and urinary excretion of mineralocorticoids. Perindopril abolished the pressor response to angiotensin I, whereas plasma ACE was only partly (-56%) decreased. It also increased plasma renin activity and did not alter the urinary excretion of steroids. Both immunization and perindopril allowed the blood pressure of SHR to return to the level of WKY-S rats and reduced the left ventricular weight. These decreases were associated with an elevated sympathetic nervous system activity as indicated by increases in the urinary excretion of catecholamines and their metabolites. It is conclude that, apart from an unaltered steroid synthesis, most of the cardiovascular effects of chronic ACE inhibition are similar to those of antirenin immunization, thus indicating that blockade of the circulating and renal renin-angiotensin system accounts for most of the effects of ACE inhibitors.
Hypertension 1990 Jul
PMID:Antirenin immunization versus angiotensin converting enzyme inhibition in rats. 219 42

Perindopril is a non-sulphydryl, pro-drug, ACE inhibitor. Following oral dosing, peak concentrations of the active moiety, perindoprilat, are achieved after 2-3 hours and perindoprilat is barely detectable by 24 hours. In contrast, maximal ACE inhibition is observed 4-6 hours after oral dosing and substantial inhibition persists beyond 24 hours. Inhibition of ACE is dose-dependent over the range 1-16 mg perindopril orally, and is mirrored by elevation of plasma renin activity and falls in aldosterone concentrations. Blood pressure reductions have been confirmed in normotensive and hypertensive subjects with maximal effect 6-10 hours after dosing and adequate antihypertensive activity at 24 hours. Blood pressure reductions are greater in the elderly than in young subjects due to pharmacokinetic differences. Dose reduction is required in elderly subjects and those with renal impairment. The antihypertensive efficacy of perindopril 4-8 mg once daily, is comparable to that of atenolol 50-100 mg once daily, captopril 25-50 mg twice daily or a hydrochlorothiazide/amiloride combination. Reduction in heart failure severity has also been reported. Perindopril appears to be a safe and effective agent for use in hypertension.
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PMID:Clinical pharmacology of perindopril. 228 58

The angiotensin-converting enzyme (ACE) inhibitors are effective in the treatment of hypertension and congestive heart failure. They improve the quality of life when compared with other conventional antihypertensive drugs. Perindopril, a new ACE inhibitor, is well tolerated and associated with fewer side effects than other types of antihypertensive agents. Moreover, it does not induce adverse metabolic changes such as hyperglycaemia and/or alterations in the blood lipid profile that could negate the benefits of lowering blood pressure. In hypertensive diabetic patients, perindopril decreases microalbuminuria without affecting the quality of glycaemic control and thereby may delay the progression of nephropathy. Therefore, perindopril appears to be an alternative first-line antihypertensive agent which may be useful in hypertensive diabetics.
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PMID:Perindopril safety and tolerance in at-risk patients. 240 94


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