Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 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

It is commonly accepted that the tolerance to insulin and hyperglycemia of the patients with non-insulin dependent diabetes mellitus (NIDDM) is due to some defect of insulin receptors or disturbances in the signaling pathway of the cell. This disease is often accompanied by hypertension. In this paper the high activity of plasma kallikrein-kinin system (KKS) (kallikrein activity was 6-8 times higher than normal), of angiotensin-converting enzyme (ACE) (4 times greater than normal), and of leukocyte elastase (2.7 times higher than normal) were demonstrated in plasma of patients with NIDDM. Increasing of KKS activity was coincident with rising of ACE activity, which may be the cause of the fast bradykinin inactivation and arising of hypertension. The treatment with ACE inhibitor during 3 months (4 mg of Perindopril per day) decreased ACE activity in patients' plasma which was accompanied with decreasing of the arterial pressure and some restoration of the carbohydrate metabolism indicators. The hyperinsulinemic euglycaemic clamping of 7 patients with NIDDM and essential hypertension showed that ACE-inhibitor (Perindopril, 4 mg) prevented bradykinin from destruction and increased the glucose consumption by tissues. The high activity of polymorphonuclear leukocytes and secretion of the elastase in NIDDM patients' plasma and/or instability of plasmatic and granular membranes of leukocyte in conditions of hyperglycaemic plasma are probably the cause of endothelial irritation and high ACE secretion. Secondly, the leukocyte may be the cause of injuring and decreasing of susceptibility of the cell receptors for insulin and bradykinin.
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PMID:[Possible participation of angiotensin-converting enzyme and leukocyte elastase in the pathogenesis of insulin-independent diabetes mellitus]. 963 24

Endothelium-dependent/nitric oxide (NO)-mediated vasodilation is impaired in hypertensive individuals. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is synthesized by many types of cells including vascular endothelial cells. The serum level of ADMA is elevated in patients with essential hypertension, but the mechanism for this increase is unknown. Therefore, the present study examined whether the renin-angiotensin system (RAS) is involved. Patients with essential hypertension [systolic blood pressure (BP) > 160 mmHg and/or diastolic BP > 95 mmHg] were randomized to an angiotensin-converting enzyme (ACE) inhibitor treatment group (perindopril, 4mg/day for 4 weeks, n = 7), an angiotensin II type 1 (AT1) receptor antagonist treatment group (losartan, 50 mg/day for 4 weeks, n = 7) or a beta-blocker treatment group (bisoprolol, 5 mg/day for 4 weeks, n = 7). Before and after the treatment, BP, serum concentration of ADMA and plasma concentration of von Willebrand factor (vWF, a biological marker of endothelial injury) were measured. Perindopril, losartan and bisoprolol decreased BP to a similar extent, and either perindopril or losartan, but not bisoprolol, significantly decreased serum ADMA and plasma vWF. These findings suggest that the RAS may contribute to the mechanism of increased serum ADMA as well as to the endothelial injury observed in hypertensive patients. The vasculoprotective actions of ACE inhibitors or AT1 receptor antagonists may be explained at least in part by amelioration of the endothelial injury through a decrease in the serum ADMA concentration.
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PMID:Renin-angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension. 1154 74

Perindopril is the newest angiotensin-converting enzyme inhibitor to be approved in the United States. It is indicated for the treatment of essential hypertension either alone or in combination with other antihypertensives, especially thiazide diuretics. Perindopril must be converted to perindoprilat, its active metabolite. The drug's prolonged duration of action allows for once daily administration. This article reviews clinical trials performed using perindopril alone and in combination to treat essential hypertension. The use of perindopril for congestive heart failure is reviewed. The influence of perindopril on arterial wall properties is discussed. Tolerability, drug interactions, and dosage and administration of the drug are reviewed.
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PMID:Perindopril. 1172 96

To compare the effect of antihypertensive drugs on endothelium-dependent vasodilation in the peripheral conduit arteries of patients with essential hypertension, in a prospective, randomized, parallel group study, endothelial function was assessed in 168 hypertensive patients before and after 6-month treatment with randomly assigned nifedipine GITS (30 to 60 mg, n=28), amlodipine (5 to 10 mg, n=28), atenolol (50 to 100 mg, n=29), nebivolol (5 to 10 mg, n=28), telmisartan (80 to 160 mg, n=29), and perindopril (2 to 4 mg, n=28). If necessary, hydrochlorothiazide (25 mg) was added to each compound. We evaluated brachial artery flow-mediated, endothelium-dependent dilation (high-resolution ultrasound) compared with endothelium-independent response to glyceryl trinitrate (25 microg/s). Brachial artery diameter was measured by automatic computerized analysis. Forty healthy subjects were evaluated as a control group. Oxidative stress production was evaluated by measuring plasma malondialdehyde and plasma lipoperoxides; plasma antioxidant capacity was assessed as ferric-reducing antioxidant power. Hypertensive patients showed a significantly (P<0.01) lower flow-mediated dilation (5.2+/-1.9%) as compared with healthy control subjects (7.1+/-2.6%). Response to glyceryl trinitrate was similar in control subjects and patients. At baseline, blood pressure, diameter, flow-mediated dilation, and response to glyceryl trinitrate were similar in the different treatment groups. All treatments similarly reduced blood pressure, but only perindopril increased flow mediated dilation (from 5.1+/-2 to 6.4+/-2.4%; P<0.01) without modifying the response to glyceryl trinitrate. Perindopril but also telmisartan nifedipine and amlodipine reduced oxidative stress and increased plasma antioxidant capacity. In patients with essential hypertension, ACE inhibitors appear to be the only compounds able to improve conduit artery endothelium-dependent vasodilation.
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PMID:Different effect of antihypertensive drugs on conduit artery endothelial function. 1271 41

Hypertension is associated with reduced coronary vasodilatory capacity, possibly caused by structural changes in the coronary resistance vessels. Because vasodilatory treatment may correct abnormal structure better than nonvasodilating treatment, we compared whether long-term angiotensin-converting enzyme (ACE) inhibition has a greater effect on coronary reserve and cardiovascular structure than beta-blockade in patients with essential hypertension. Thirty previously untreated hypertensive patients were randomized in a double-blind design to treatment for 1 year with either perindopril (4 to 8 mg per day, n=15) or atenolol (50 to 100 mg per day, n=15) and furthermore compared with normotensive controls. Cardiac output and left ventricular mass were measured with echocardiography and resistance artery structure was determined in vitro. Using positron emission tomography, myocardial perfusion (MP) was determined at rest and during dipyridamole-induced hyperemia while still on medication. Perindopril reduced left ventricular mass by 14+/-4% (P<0.01), peripheral vascular resistance by 12+/-6% (P<0.01), and media thickness-to-lumen diameter ratio of resistance arteries by 16+/-4% (P<0.05), whereas atenolol had no effect. Resting MP was decreased both by perindopril (-11+/-4%, P<0.01) and by atenolol (-25+/-4%, P<0.01) in parallel to the reduction in rate pressure product. Hyperemic MP was unaltered by perindopril (+2+/-6%, P=NS), but reduced by atenolol (-32+/-5%, P<0.01). Compared with atenolol, perindopril treatment resulted in higher coronary reserve (P<0.05). We conclude that compared with beta-blockade, ACE inhibition increases coronary reserve and results in regression of hypertensive resistance artery structure and left ventricular hypertrophy. Vasodilating may thus be superior to nonvasodilating treatment in repairing the hypertensive myocardial microcirculation.
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PMID:Myocardial perfusion during long-term angiotensin-converting enzyme inhibition or beta-blockade in patients with essential hypertension. 1532 83

Structural and functional changes in large and small arteries in hypertension, even at early stages, may affect one or several end organs such as the brain, heart, and kidneys, contributing to cardiovascular morbidity and mortality. Therefore, modern treatment strategies should not only target blood pressure (BP) reduction but also normalize vascular structure and function. The purpose of this article is to review the large body of evidence, from randomized double-blind clinical trials, that has been gathered in regard to the angiotensin-converting enzyme (ACE) inhibitor perindopril, demonstrating its efficacy in reducing BP, reversing abnormalities of vascular structure and function in patients with essential hypertension, and ultimately preventing cardiovascular events. At the site of small resistance arteries, long-term treatment with perindopril, but not atenolol, reduced arterial wall hypertrophy for a given BP reduction. The improvement in small artery function in response to structural changes is exemplified at the site of the coronary circulation. Perindopril increased coronary blood flow and coronary reserve, in parallel with the regression of periarteriolar and interstitial collagen of coronary arterioles. At the site of large arteries, long-term treatment with perindopril reduced carotid and radial artery wall hypertrophy, and reduced carotid artery internal diameter. In response to these structural changes, large artery function improved at the site of the carotid and brachial arteries, showing a higher arterial distensibility, and at the site of the coronary circulation, showing a normalized arterial dilation in response to a cold pressor test or an increase in blood flow. Moreover, in patients with end-stage renal disease, perindopril decreased pulse wave velocity independently of BP changes, resulting in a highly significant relative risk reduction in all-cause and cardiovascular mortality. The multifactorial antiatherosclerotic profile of perindopril suggests a beneficial effect not only in patients with uncomplicated hypertension but also in patients with established coronary heart disease or previous stroke, as exemplified by the EUropean trial on Reduction Of coronary events with Perindopril in stable coronary Artery disease (EUROPA) and the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS).
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PMID:Evidence for benefits of perindopril in hypertension and its complications. 1612 52

Perindopril is a third-generation ACE inhibitor that is characterised as a small, lipophilic molecule with a therapeutically active carboxyl side group. These and other features combine to make this a unique member of a very well-established class of drugs that have proven efficacy in a wide range of cardiovascular diseases. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) demonstrated benefit in the secondary prevention of patients with stroke, whereas the Perindopril and Remodelling in Elderly with Acute Myocardial Infarction (PREAMI) trial supports extended routine use after myocardial infarction. The most recent evidence from the European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease (EUROPA) and the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) show that perindopril is able to improve the prognosis of patients with a relatively low global cardiovascular risk, denoted either by the presence of stable coronary artery disease or of essential hypertension in conjunction with at least three other risk factors. The fact that major relative risk reductions have been reported for these two studies is matched by the significance of the findings to modern clinical practice. Both studies were conducted in the context of advance concomitant care that is typically better in clinical trials than in routine practice. In particular, the benefits observed were seen to be of a similar magnitude, and also independent of those resulting from statin therapy. Of particular interest is the likely complimentary action of these treatment strategies with regard to the stabilisation of atheromatous plaques. Perindopril is a well-established drug, the full value of which is only now becoming fully apparent.
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PMID:Perindopril. 1637 Sep 23

Monotherapy prevailing nowadays in the treatment of essential hypertension is one of the causes of not sufficiently effective hypotensive therapy. Combination of antihypertensive drugs is a more efficient strategy as synergism of applied medications may be reached and not high doses may develop less adverse effects. 30 patients (17 men and 13 women, average age is 51 years) with hypertension which have not taken antihypertensive drugs from different reasons have been prescribed Noliprel being a combination of Perindopril and Indapamid in low doses (2.00 mg and 0.625 mg accordingly) for 3 months. The study conducted by the author differs from the trials on Noliprel effectiveness by its more profound investigation of the echocardiography parameters and cardial hemodynamics. The measurement of left ventricular myocardium mass index, wall and interventricular septal thickness and many other echocardiographic parameters have been studied. Noliprel has already demonstrated good antihypertensive activity in 83.3% of patients after one month therapy. 16.7% of patient increased dose intake to two pills per day and after 3 months of the therapy their arterial pressure reached the target level. The author considered in details the dynamics of echocardiography parameters during therapy with Noliprel. Noliprel is a highly effective and safe medication which positively influences on processes of myocardium remodeling and is metabolically neutral. No side effects have been seen during the treatment with this medication by the patients having been treated.
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PMID:[Noliprel efficiency in patients with hypertension]. 1710 Jan 89

Hypertension has been associated with changes in endothelial function in both large muscular arteries and small resistance arteries. We evaluated the relationship between blood flow velocity and dilatation of the brachial artery following transient forearm ischemia and acetylcholine-induced relaxation in subcutaneous small arteries and the influence of antihypertensive therapy on both in patients with essential hypertension. Thirty-one previously untreated hypertensive patients were randomized in a double-blind fashion to treatment with either the angiotensin-converting enzyme (ACE) inhibitor perindopril or the beta-blocker atenolol and compared with 17 healthy normotensive controls. Before and after 1 year of treatment, while still on active medication, flow-mediated dilatation (FMD) was measured in the brachial artery using ultrasound while relaxation to acetylcholine in small arteries was tested in vitro in a myograph. FMD correlated inversely to resting brachial artery diameter (r = -0.38, p<0.05). FMD corrected for resting diameter (FMD(corr)) was lower in patients (3.0+/-0.2%) compared with controls (4.2+/-0.3%, p<0.01). In both patients and controls, FMD(corr) was related to flow velocity in a non-linear way with FMD(corr) reaching a maximum despite increasing flow velocities, and in the patients, FMD(corr) was only reduced at high flow velocities. Furthermore, patients had a reduced acetylcholine-induced relaxation in small arteries (p = 0.04). Perindopril and atenolol reduced blood pressure to similar levels and both drugs improved FMD(corr) to a similar degree without any effects on relaxation to acetylcholine in small arteries. The present study demonstrates the role of correcting for differences in baseline diameter during measurements of FMD and a non-linear relationship between flow velocity and FMD in the brachial artery. Furthermore, the results suggest different effects of antihypertensive treatment on endothelial function in large and small arteries.
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PMID:Large and small artery endothelial function in patients with essential hypertension--effect of ACE inhibition and beta-blockade. 1761 9


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