Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exogenous obesity is characterized hemodynamically by expanded intravascular (plasma) volume associated with an increased cardiopulmonary volume and cardiac output. In contrast, essential hypertension is related to an increased total peripheral resistance that is more or less uniformly distributed throughout the component organ circulations associated with a contracted plasma volume in proportion to the height of arterial pressure. Thus, both cardiac output and total peripheral resistance are elevated in obesity hypertension, and both impose a load on the left ventricle, resulting in both a volume and a pressure overload left ventricular hypertrophy. Although renal vascular resistance is not as increased as it is in lean hypertensive patients, these patients are subjected to hyperfiltration and proteinuria. Additionally, these hemodynamic alterations coexist with carbohydrate intolerance, hyperinsulinemia, hyperlipidemia, and hyperuricemia. With weight reduction and associated pressure reduction, the hemodynamic and metabolic changes reverse toward normal. However, should this not be achievable, the angiotensin converting enzyme inhibitors and calcium antagonists provide rational physiological approaches to drug therapy. With these agents pressure reduction is achieved through a fall in vascular resistance without intravascular volume expansion, and this is associated with reduced left ventricular mass and preserved cardiac and renal function, and without exacerbation of preexisting metabolic perturbations. Hence, these two classes of antihypertensive agents may provide a rational and physiological means for reversing the pathophysiological alterations of hypertensive disease in those obese patients in whom weight control is not possible.
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PMID:Obesity hypertension. Converting enzyme inhibitors and calcium antagonists. 173 Apr 48

The most common cause of death in hypertensive patients is myocardial infarction (MI), being three times more common than stroke. Lowering raised BP results in 40% fewer strokes, but only 14% fewer MIs. This may be because other coronary risk factors that often accompany hypertension (e.g. obesity, lipid and thrombotic disturbances, insulin insensitivity, increased plasma renin activity and increased sympathetic activity) are either unaffected or exacerbated by some of the traditional antihypertensive agents. Some of these risk factors show a diurnal rhythm peaking at 07.00-10.00 hours, thus this time constitutes a 'vulnerable period' for sudden death or death from MI. beta-blockers and diuretics have been effective in preventing stroke, but diuretics (at least potassium-losing diuretics) might actually increase the incidence of sudden death and MI in young to middle-aged hypertensive subjects (though elderly patients may benefit). Quality of life can be impaired by some beta-blockers, and diuretics can cause metabolic upset and male impotence. Thus, antihypertensive agents that are not only effective and well tolerated but are beneficial to the broader coronary risk profile are desirable. ACE inhibitors should prove particularly useful in terms of: good quality of life; non-exacerbation or improvement of coronary risk factors; treating patients with impaired left ventricular function; reversing left ventricular hypertrophy and vascular wall hypertrophy, thus improving coronary flow reserve; atheroma regression; renal protection, particularly in diabetes; and prevention or regression of LV dilatation (remodelling) following MI.
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PMID:What does the future hold for ACE inhibitors? 179 18

Hemodynamic and structural changes of the heart and large arterial vessels were studied in normotensive and spontaneously hypertensive rats following 12-week administration of converting enzyme inhibitor (perindopril, 2 mg/kg daily by gavage). In both strains, a significant blood pressure reduction was observed. In normotensive rats, the hemodynamic changes involved significant increase in systemic arterial compliance, whereas slight changes in left ventricular weight and aortic medial thickness were observed. In hypertensive rats, the increase in compliance was relatively small, whereas there was a major reduction in medial thickness. The reduction of the media thickness was much more pronounced than that of the left ventricular hypertrophy. In both strains, the collagen density in the subendocardial layers of the left ventricle was significantly decreased in treated vs untreated groups. The isomyosine profile of the left ventricular muscle was also modified by ACE inhibition with an increase in the V1 form and a decrease in the V3 form. The present results suggest that the cardiac and arterial changes observed following long-term converting enzyme inhibition do not strictly parallel the blood pressure changes in hypertensive rats. Dissociation between cardiac and arterial changes may be observed.
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PMID:Angiotensin converting enzyme (ACE) inhibitors in experimental hypertension: influence on heart and arteries. 182 84

Models of right ventricular hypertrophy in rats have been created and characterized: Daily injections of triiodothyronine, irradiation of the lung in Brown-Norway rats, chronic myocardial infarction, and pulmonary artery stenosis. A new Millar ultraminature catheter pressure transducer designed for right heart catheterization allowed the measurement of right ventricular function. All models were characterized by an increase in right ventricular systolic pressure, by an elevation in the RNA/DNA ratio in the right ventricle, and by an increase in the right ventricular weight/body weight ratio. Myocytes isolated from the right ventricle 4 weeks after coronary artery ligation had a greater volume and cross sectional area. Similar results were obtained 14 days after pulmonary artery stenosis. In this model, the effect of angiotensin converting enzyme inhibition with ramipril (1 mg/kg, daily) was examined. The increase in right ventricular systolic pressure from 35 +/- 2 mm Hg to 61 +/- 4 mm Hg (without ramipril) was not influenced by ramipril (63 +/- 4 mm Hg), neither was the elevation of right ventricular weight. However, the increase in cell volume and cross-sectional area of myocytes isolated from the right ventricle was less pronounced in the ramipril-treated group (+27% compared to +58% in untreated animals). Thus, angiotensin converting enzyme inhibition with ramipril altered the hypertrophic response at the cellular level.
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PMID:[Right ventricular hypertrophy in rats: effect of ACE inhibitors]. 183 Sep 10

Epidemiologic studies have revealed that in arterial hypertension left ventricular hypertrophy is an important risk factor for cardiac failure. Accordingly antihypertensive therapy should aim at preventing or regressing left ventricular hypertrophy. Reduction of blood pressure does not necessarily induce reversal of left ventricular hypertrophy. Vasodilators like hydralazine and minoxidil, which lead to augmented plasma levels of norepinephrine, were not able to diminish left ventricular hypertrophy. In contrast, a sympatholytic therapy with methyldopa caused a reversal of left ventricular muscle mass. These experimental findings in spontaneously hypertensive rats led to the hypothesis that catecholamines control the onset and progression of myocardial hypertrophy mostly independent of blood pressure. This hypothesis was supported by the experimental findings, that subhypertensive dosages of norepinephrine induce left ventricular hypertrophy and that this hormone promotes alpha-receptor mediated growth of isolated myocytes. Recent studies have revealed that also the renin-angiotension-system has trophic effect on the myocardium. Clinical investigations have documented regression of cardiac hypertrophy due to antihypertensive therapy with sympatholytic drugs, ACE-inhibitors, calcium-channel blockers and beta-receptor blockers. Diuretics failed to decrease left ventricular muscle mass along with blood pressure normalization.
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PMID:[ACE inhibition: mechanisms of cardioprotection in heart hypertrophy]. 183 Sep 11

To compare the efficacy of new calcium blocker nitrendipine and ACE-inhibitor captopril on the regression of hypertensive left ventricular hypertrophy (LVH), 134 hypertensive subjects with LVH were divided randomly into two groups. 2DE, M-mode and pulsed Doppler echocardiography was used to measure the left ventricular structure and function. In the nitrendipine group (n = 67, mean age 48 +/- 11 years), nitrendipine (20-40 mg/day) was administered for 24 months, and in the captopril group (n = 67, mean age 47 +/- 12 years), captopril (75-150 mg/day) was also given for 24 months. Blood pressure decreased significantly in all the patients. In the nitrendipine group, the thickness of the interventricular septum (IVST) and the posterior wall of the left ventricle (PWT) as well as the left ventricular mass index (LVMI) decreased by 20.3%, 15.5% and 25.7% (P less than 0.01) respectively. The cardiac index (CI), left ventricular ejection fraction (EF) and fractional shortening (FS) remained unchanged. The early peak filling velocity (E, 0.64 +/- 0.15 to 0.86 +/- 0.22, P less than 0.01) of the mitral valve and E to late peak filling velocity ratio (E/A, 0.88 +/- 0.20 to 1.31 +/- 0.31, P less than 0.01) increased significantly. In the captopril group, IVST, PWT, and LVMI were 20%, 17.1% and 23.6% respectively (P less than 0.01). CI (2.6 +/- 0.5 to 3.7 +/- 0.6L/min/m, P less than 0.01) and EF (60 +/- 4 to 78 +/- 6%, P less than 0.01) increased. Both E and E/A were elevated in a similar degree as in the nitrendipine group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the effects of nitrendipine and captopril on the regression of hypertensive left ventricular hypertrophy. 183 65

The cardiac organ manifestation of arterial hypertension comprises the myocardium itself with left-ventricular hypertrophy, the interstitium with perivascular and interstitial fibrosis, and the coronary circulation with disease of large and small coronary arteries. The consequences of the sum and interactions of these cardiac organ manifestations have an impact on left-ventricular systolic and diastolic function, the ischemic risk, and the occurrence of arrhythmias in hypertensive patients. As the prognosis of arterial hypertension is determined, to a considerable extent, by these cardiac complications, the aim of treatment of hypertensive heart disease is reversal of the myocardial hypertrophy in order to prevent later progression to hypertensive failure. A further goal of therapy is reversal of hypertensive coronary microangiopathy in order to improve the coronary reserve and to reduce the ischemic risk. Regression of hypertrophy can be induced by suitable antihypertensive drugs (calcium channel blockers of the dihydropyridine type, ACE inhibitors, and sympatholytic substances). While normal systolic function was maintained in the compensated stage of hypertensive hypertrophy and was not significantly influenced by antihypertensive therapy, diastolic function was impaired in a very early stage of arterial hypertension. Both the phase of isovolumic relaxation and the phase of early diastolic filling were imparied, while after long-term antihypertensive treatment with Ca-channel blockers of the dihydropyridine type or ACE inhibitors, only the latter one was improved. From preliminary results there is clinical evidence that hypertensive disease of small coronary arteries can be reversed after long-term antihypertensive treatment with a consequently improved coronary reserve and a reduced ischemic risk. Moreover, to what extent the prognosis of hypertensive heart disease can be improved by reversal of myocardial hypertrophy and disease of small coronary arteries is yet unknown.
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PMID:Long-term treatment in arterial hypertension for protecting hypertrophic myocardium. 183 50

Changes in left ventricular remodeling due to antihypertensive therapy have been demonstrated in experimental animal studies although no quantitative relationship has been shown between correction of blood pressure and regression of myocardial mass. As regards the qualitative aspects of regression, only the ACE inhibitors have been shown to prevent the development and induce regression of the excess collagen content of the myocardium submitted to chronic pressure overload. The problems posed by remodeling in clinical practice are more complex: should regression of myocardial mass itself be the therapeutic objective in the absence of a practical method of analysing the interstitial factor of hypertensive disease or should we concentrate on the satellite problems of hypertrophy which are correction of ischemia, left ventricular filling abnormalities and arrhythmias. For each of these clinical problems, the benefits attributed to changes in remodeling, though probable, are to a large degree hypothetical. The benefits offered by these drugs which reduce ventricular hypertrophy are, however, considerable.
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PMID:[Left ventricular remodeling and hypertension. Course with antihypertensive therapy]. 183 22

The heart is one of the major target organs that becomes secondarily involved with the unrelenting and progressive vascular disease of essential hypertension. As a result of this increasing afterload that is imposed upon the left ventricle, the ventricular chamber adapts structurally and functionally. Structural changes involve an increase in muscle mass that is achieved through left ventricular hypertrophy (in a manner similar to the arteriolar changes demonstrated by increased thickening). Unless antihypertensive therapy is interdicted in this disease process, left ventricular failure will ensue as the major cardiac hemodynamic consequence. Left ventricular hypertrophy is also associated with a risk that is independent of the pressure overload and hemodynamic risk. Although antihypertensive therapy will reduce from the hemodynamic alterations, only recently have epidemiological findings suggested that the independent risk of LVH may be reduced with pharmacological therapy. There are no data available to indicate just which agents may reduce the risk from LVH; but relatively recent studies seem to indicate that while all agents may reduce LVH with prolonged therapy only certain classes of agents will do so independent of their hemodynamic factors. Some of these agents, however, may impair cardiac function if arterial pressure is increased abruptly following therapeutic reduction of cardiac mass. Other agents may preserve normal function--or even may improve function. Among those classes of antihypertensive agents that reduce cardiac mass at least in part due to nonhemodynamic factors, are the angiotensin converting enzyme inhibitors, the calcium antagonists, and most adrenergic inhibitors. Evidence will be presented demonstrating the hemodynamic/structural dissociation of those pharmacological agents that reduce cardiac mass with short-term treatment in spontaneously hypertensive rats with left ventricular hypertrophy. Although centrally active adrenolytic, angiotensin converting enzyme (ACE) inhibitors, and calcium antagonists all reduce cardiac mass, their structural and cardiac functional effects differ greatly. Even within the ACE inhibitor group their effects vary--improving, impairing, or not changing the Frank-Starling relationships following reduction in left ventricular mass. We postulate great variability of cardiac intramyocytic penetrance of the pharmacological agents and their local intracellular effects on mitogenesis of the ventricular myocyte. The implications on cardiac function and therapy have vast potential. Therefore, current investigative areas involving new concepts of molecular biology of the cardiac myocyte may provide great promise to the quest of unraveling some of the newly postulated questions: What is the role of ionized intracellular calcium? Do the local renin-angiotensin systems in the cardiac and vascular myocyte participate in the development and regression of hypertrophy?(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Left ventricular hypertrophy: dissociation of structural and functional effects by therapy. 183 47

Arterial hypertension is often complicated by left ventricular hypertrophy (LVH) and by vascular structural changes resulting in decreased proximal and distal compliance. LVH is an adverse prognostic factor because it increases the incidence of sudden death and other morbid events related to ischaemic heart disease, whereas vascular alterations may induce target organ damage and contribute to the maintenance of elevated blood pressure values. Thus, antihypertensive treatment must both reduce blood pressure and halt regression of cardiovascular structural changes. A review of the literature suggests long-term use of calcium antagonists, ACE inhibitors, and beta-blockers may revert LVH. We have found that such long-term drug use not only reduces blood pressure and LVH, but also ventricular arrhythmias that are often related to cardiac hypertrophy; however, diuretics do not have this beneficial effect. As regards vascular disturbances ACE inhibitors partially revert these alterations, whereas beta-blockers do not. Further studies are needed to determine whether there are regional differences in the regression of cardiovascular structural changes or whether different antihypertensive drugs have different effects on these changes.
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PMID:Cardiovascular structural changes in hypertension: possible regression during long-term antihypertensive treatment. 183 19


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