Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We had previously reported that sinoaortic denervation induces cardiac ventricular hypertrophy in rats. The objective of the present study was to determine whether this cardiac hypertrophy can be prevented by inhibition of angiotensin converting enzyme (ACE) with captopril, 20 mg/kg, administered sc twice daily for 15 days. The left ventricular weight/body weight ratio significantly increased (12%) in sinoaortic denervated (SAD) rats 15 days after surgery when compared with the sham-operated group (SO). Administration of captopril to SAD rats prevented this ventricular hypertrophy and decreased but did not completely abolish their high arterial pressure. No changes in the normal pattern of baroreceptor reflex activity were observed in the captopril-pretreated SAD or SO groups. These data suggest the participation of the angiotensin system in the development of cardiac hypertrophy in SAD rats.
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PMID:Captopril prevents ventricular hypertrophy in sinoaortic denervated rats. 184 Apr 24

The major differences that have been recognized between black and white hypertensives are primarily epidemiologic, with hypertension being more prevalent, having an earlier onset, and having more severe sequelae in the black population. The cause of the problem in both black and white people remains obscure, but it appears that a difference in sodium handling may contribute to the particular hemodynamic and hormonal profile of black hypertensives. Salt sensitivity, expanded plasma volume and low renin levels have been the hallmark of the black hypertensive. Complications such as stroke and left ventricular hypertrophy remain the major sequelae of this disease in blacks. Finally, a current study confirmed the improved efficacy of antihypertensive therapy in blacks to diuretics and calcium channel blockers and a somewhat lower efficacy profile to angiotensin converting enzyme inhibitors and beta blockers, although the latter classes of agents have shown better response in blacks than previously thought.
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PMID:Hypertension in blacks. 194 90

There is evidence from experiments in animals, biological and molecularbiological investigations, that extra-renal renin-angiotensin systems may have important implications in the pathogenesis of various diseases, in particular in regard to the development of hypertrophy in smooth muscle cells of blood vessels and in the myocardium. Thus, it is getting more likely, that angiotensin II is an endogenous growth factor. We have recently shown, in an animal model of left ventricular hypertrophy (aortic stenosis due to a silver clip on the aorta ascendens), that chronic application of an ACE-inhibitor results in a nearly complete regression of left ventricular hypertrophy even under the conditions of an unaltered afterload. The extent of the regression of left ventricular hypertrophy was not statistically different from animals in which the regression of hypertrophy was achieved by removal of the clip. According to these results, we demonstrated for the first time, that the renin-angiotensin system plays a major role in the maintenance of left ventricular hypertrophy and that after the inhibition of the system, a considerable regression of left ventricular mass can be achieved which is independent from hemodynamic factors.
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PMID:[Angiotensin-converting-enzyme inhibitor and heart hypertrophy]. 213 56

Because left ventricular hypertrophy (LVH) is a strong risk factor for cardiac morbidity and mortality considerable interest has been generated concerning the possible effects of modifying LVH in hypertensive patients. In animal models disproportionate regression of left ventricular (LV) mass in relation to blood pressure may produce adverse effects on coronary blood flow reserve or LV systolic function. Clinical studies of modulation of LVH with antihypertensive drug therapy have been of two types: (1) large scale community comparison trials in which the prevalence of LVH and its regression were evaluated serially by electrocardiography (ECG) with stepped care drug therapy and (2) relatively short term (less than 2 years) studies with echocardiographic (ECHO) determination of LVH. The development of anatomically validated measurement of LV muscle mass by ECHO has demonstrated ECHO to be much more sensitive than ECG to assessment of LVH. Community comparison trials of stepped care therapy such as the Multiple Risk Factor Intervention Trial (MRFIT) and Hypertension Detection and Followup Study (HDFP) have not had the statistical power to demonstrate significant effects on risk reduction despite evidence for significant decrease in ECG-LVH despite participant numbers in the range of 8,000 to 10,000 followed serially for 5 to 6 years. Analysis of over 60 studies of hypertensive treatment using ECHO for assessment of LVH mass changes, averaging 10 to 15 subjects/study, indicates that correlation of reduction of LV mass with decrease in blood pressure has been weak (r = 0.255, P less than .025). Drug monotherapy studies have shown that use of calcium channel blockers and angiotensin converting enzyme inhibitors predominantly decrease LV mass.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical studies of drug reversal of hypertensive left ventricular hypertrophy. 214 30

Cardiac hypertrophy in essential hypertension is documented to be an independent risk factor for congestive heart failure, coronary heart disease and cardiac sudden death. Reduction of left ventricular hypertrophy therefore emerged as a new challenge of antihypertensive treatment. Sympatholytic agents, calcium entry blockers, and angiotensin converting enzyme inhibitors have been found to reduce left ventricular hypertrophy, whereas vasodilators (and most likely also diuretics) are unable to reduce left ventricular mass despite good control of arterial hypertension. Several studies indicated that reduction of left ventricular hypertrophy is not detrimental to cardiac pump function: systolic and diastolic function were found to be maintained at rest and during exposure to increased pressure load. In hypertensive patients with left ventricular hypertrophy ventricular arrhythmias have been reported to be increased and to be the pathophysiological link for the increased risk of cardiac sudden death. Reduction of cardiac hypertrophy was found to be accompanied by a reduction of prevalence and severity of ventricular arrhythmias if treated with betablockers, calcium entry blockers or converting enzyme inhibitors. Whether reduction of cardiac hypertrophy indeed decreases the cardiovascular risk attributed to left ventricular hypertrophy is unknown at present, although clinical studies support such a viewpoint.
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PMID:Risk reduction following regression of cardiac hypertrophy. 214 97

Several experimental models involving the development of cardiac hypertrophy in adult rats are characterized by the reexpression of the fetal isoform of myosin heavy chain (V3). To determine whether a similar adult-to-fetal shift in the expression of the thin-filament proteins occurs during cardiac hypertrophy, we have examined the expression of the isoforms of myosin, tropomyosin, and troponin T in the left ventricle of young spontaneously hypertensive rats (SHR) with and without treatment using enalapril, an angiotensin converting enzyme inhibitor. Phosphorylation of tropomyosin, which is predominant in the fetal state, was also analyzed. Twelve-week-old SHR were treated with enalapril for 2, 5, 8, and 9 weeks followed by withdrawal of treatment for 9 weeks. Control SHR, without drug treatment, were weight- and age-matched. After 9 weeks of enalapril treatment, mean arterial blood pressure was reduced (from 166 +/- 11 to 89 +/- 5 mm Hg), and left ventricular weight/body weight ratio was regressed (from 2.53 +/- 0.14 to 1.96 +/- 0.05 g/kg) to normotensive levels. During the 9-week treatment period, the percent V3 decreased in SHR substantially from 35 +/- 3% to 13 +/- 1%. There was a significant correlation between the left ventricular hypertrophy and the percent V3 myosin expression in the SHR during regression (r = 0.697, p less than 0.001). However, only the adult isoforms of tropomyosin and troponin T were detected in the SHR with or without enalapril treatment, and the level of tropomyosin phosphorylation remained constant irrespective of the degree of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regression of cardiac hypertrophy in spontaneously hypertensive rats by enalapril and the expression of contractile proteins. 214 74

Some old icons of hypertension warrant questioning in view of new insights. Lowering of blood pressure is no criterion of efficacy in prevention of cardiovascular morbidity, mortality and sudden death. The drugs used in early studies - diuretics, vasodilators and reserpine - greatly improved mortality from malignant hypertension, apoplectic stroke and congestive heart failure, but had little or no effect in persons with milder degrees of elevated blood pressure, who constitute the vast majority of hypertensives. The failure of diuretics and vasodilators to influence cardiovascular disease favorably appears due not to their known adverse effects on risk factors, such as lipids, as some have held, but to a failure - in conjunction with some sympathetic blocking agents - to cause effective regression of left ventricular hypertrophy, the keystone of successful therapy. A study of 674 hypertensive persons surveyed in the United States and eastern Canada, personally examined during their visit to a Florida health resort, has shown striking changes in prescribing practice during the period surveyed (1985-88), notably with increased use of angiotensin converting enzyme (ACE) inhibitors and, to a lesser degree, increased use of calcium channel blockers. Both of these cause regression of left ventricular hypertrophy, and will hopefully show long term benefit in decreasing hypertension mortality. Left ventricular hypertrophy is detected most sensitively echocardiographically, and is worthwhile not only for estimation of prognosis, but also for guiding therapy. Left atrial hypertrophy is a mirror of left ventricular hypertrophy and may be detected echocardiographically and in the electrocardiogram.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The heart (ventricle and atrium) is the heart of hypertension, not blood pressure. 214 1

An important antecedent to the development of late congestive heart failure is left ventricular dilatation and remodeling following myocardial infarction, which occurs in 30-40% of acute anterior transmural infarcts. Dilatation and remodeling commence within the first 24 hours following myocardial infarction and may be steadily progressive over months to years. Both the infarcted and uninfarcted regions of the myocardium are equally involved in the process. The remodeling process comprises left ventricular wall thinning (mainly due to cell slippage), chamber dilatation, and compensatory hypertrophy of the uninfarcted segment of the myocardium. The hypertrophy may initially be physiologic but may ultimately become a pathologic process, and thereby contribute to pump dysfunction. The possible reasons why the ventricular hypertrophy may ultimately be dysfunctional include alterations in local architecture and their sequelae alone or in concert with local changes in the beta-adrenergic, alpha-adrenergic, or renin angiotensin systems. At the present time, there are encouraging data to suggest that nitroglycerin, or the angiotensin converting enzyme inhibitor captopril, may ameliorate this process.
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PMID:Left ventricular dilatation and failure post-myocardial infarction: pathophysiology and possible pharmacologic interventions. 214 59

Sudden death has been shown to be due in the majority of cases to ventricular arrhythmia. Left ventricular hypertrophy (LVH) may be implicated in the aetiology of some arrhythmia and sudden death. Recent evidence suggests that the relationship between LVH and arrhythmia may be complex and that there may be an interaction with serum potassium levels. ACE inhibitors have been shown to be anti-arrhythmic in heart failure. Although other vasodilators have been shown to be anti-arrhythmic, ACE inhibitors also raise serum potassium levels and this may therefore be of importance to their anti-arrhythmic activity. In LVH, their antiarrhythmic potential may be greatest in those who are potassium depleted.
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PMID:ACE inhibitors and the heart: hypertrophy reversal and antiarrhythmic effects. 214 90

When inhibitors of the renin-angiotensin system (RAS) were initially developed, they were believed to act as antihypertensive agents mainly under pathophysiological conditions, in which an elevated plasma RAS contributed to the elevation and maintenance of high blood pressure (BP). However, evidence has accumulated from studies in hypertensive patients, as well as in animals, indicating that BP could be lowered by converting-enzyme inhibitors (CEIs) independently of whether or not the plasma RAS was stimulated. Several other effects had to be considered. It was thus discovered that converting enzyme (CE) is identical with the bradykinin-degrading enzyme, kininase II, and CEIs can therefore potentiate the vasodepressor effects of bradykinin and thereby interact with the prostaglandin system. Actions of CEIs possibly unrelated to inhibition of angiotensin and kininase also need to be considered. The actions of CEIs at the tissue level (brain, heart, blood vessels, kidney, adrenal gland) and their interference with the autonomic nervous system through central and peripheral actions may under certain conditions be more important than their inhibition of the circulating hormonal plasma angiotensin II. Recent clinical and experimental studies and new insights in the molecular biology of the RAS, especially gene expression of renin and angiotensinogen in tissues of the cardiovascular system, support this view. We have found that chronic CE inhibition with substances such as captopril, quinapril and lisinopril specifically affects angiotensinogen mRNA levels in cardiovascular tissues, and has marked effects on left ventricular hypertrophy, possibly through an action on cardiac angiotensin. These findings have consequences not only for the understanding of pharmacokinetics and pharmacodynamics of CEIs but also for their practical therapeutic use.
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PMID:The role of tissue renin-angiotensin systems in hypertension and effects of chronic converting-enzyme inhibition. 216 28


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