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

The aim of the study was to compare, in a rat model of congestive heart failure, the effect of captopril, a selective angiotensin-converting enzyme (ACE; EC 3.4.15.1) inhibitor, to that of alatriopril, a mixed inhibitor of ACE and atriopeptidase (EC 3.4.24.11), an enzyme implicated in the degradation of atrial natriuretic factor (ANF). Myocardial infarction was induced by ligation of the left coronary artery. Groups of rats received orally twice daily captopril (10 mg/kg), alatriopril (100 mg/kg) or vehicle. Treatments were started 18 to 20 h after ligation and continued for 4 weeks. Hypertrophic and hormonal changes reflecting congestive heart failure were assessed in rats with large infarcts by measuring the relative weight of cardiac tissues as well as by assaying ANF in heart and plasma and by measuring renin activity in plasma. Both treatments significantly reduced cardiac hypertrophy, but alatriopril showed a greater efficacy than captopril--the increase in relative heart weight reaching 38% with captopril and only 22% with alatriopril (P < .05). The hypertrophy of right ventricle was reduced by 47% with alatriopril and by 35% with captopril (N.S.), whereas the corresponding reductions for atria were 47% vs. 21% (P < .05). Both treatments prevented the ligation-induced increase of ANF level in the right ventricle. In contrast, plasma ANF level was significantly reduced after captopril but not after alatriopril treatment, a difference that probably reflects the protection of endogenous ANF in circulation resulting from atriopeptidase inhibition. Plasma renin was increased by 36-fold after captopril but only by 1.6-fold after alatriopril, a difference that presumably reflects the inhibition of renal renin secretion by endogenous ANF after alatriopril. These data suggest that enhancement of ANF levels in circulation via atriopeptidase inhibition magnifies the capacity of ACE inhibitors to prevent cardiac hypertrophy, and they show the potential therapeutic value of mixed ACE-atriopeptidase inhibitors in congestive heart failure.
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PMID:Effects of alatriopril, a mixed inhibitor of atriopeptidase and angiotensin I-converting enzyme, on cardiac hypertrophy and hormonal responses in rats with myocardial infarction. Comparison with captopril. 803 46

Hypertrophic cardiomyopathy (HCM) is a disease with different etiological, morphological, functional, clinical and therapeutic aspects. Recent investigations indicate that HCM is considerably widespread in the population (1:500). The causes seem to generate from familial or sporadic abnormalities (mutations). Depending on the clinical aspect, the complaints, and on the basis of morphologic and hemodynamic investigational results, we mainly have to consider two types of medical and surgical management. 1. Hypertrophic nonobstructive cardiomyopathy (HNCM) Patients may have no hemodynamic or morphologic deviations, but may be identified by familial moleculargenetic investigations. Others may have different types of rhythm disturbances which may indicate a higher risk of sudden death. Depending on the degree of hypertrophy, the clinical impairment indicates medical therapy with beta-blockers, Ca antagonists, and antiarrhythmic drugs. In the case of clinical deterioration and manifestation of myocardial insufficiency diuretics, digitalis, ACE inhibitors, and catecholamines are indicated. Further impairment may lead to heart transplantation or as a bridging procedure to implantation of a left ventricular or biventricular assist device until a suitable donor heart is available. 2. Hypertrophic obstructive cardiomyopathy (HOCM) Symptomatic patients may have different localizations of the left ventricular outflow tract obstruction (LVOTO) in the subaortic area (typical form) and in midventricular position of the LV (atypical form). The first therapeutic step is always medical therapy with beta-blockers, Ca antagonists, and antiarrhythmic drugs. Further deterioration toward clinical class III (NYHA) despite long-term medication until recently was generally accepted as indication for transaortic subvalvular myectomy (TSM). Today mostly two other techniques are preferred--if possible Double chamber pacing (DCP) (atrial triggered ventricular pacing), Transcoronary ablation of septal hypertrophy (TASH) (by selective injection of alcohol, 95%, into the first septal branch). Especially in younger patients, after syncope, life-threatening tachyarrhythmias, and after resuscitation, the implantation of a cardioverter defibrillator may be necessary. Comparative prospectively randomized studies between different therapeutic regimens for HOCM are not available. Retrospective analyses of patients after TSM show a considerable clinical improvement. The risk of sudden death is relatively low, but not excluded. Patients after TSM demonstrate advantages concerning the survival rate despite the more deteriorated condition against those after medical therapy only. According to the new interventional techniques, long-term results are not yet available, of course. However, the long-term results after TSM may serve as a comparative standard which have at least to be reached by DCP and/or TASH.
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PMID:[Hypertrophic cardiomyopathy (HCM). Surgical versus drug therapy]. 1035 66

Blood vessels are remodeled in hypertension both structurally and functionally. The changes that occur in their structure, mechanical properties, and function contribute to blood pressure elevation and to complications of hypertension. We studied the remodeling of small arteries in experimental animals and humans. Smooth muscle cells of small arteries are restructured around a smaller lumen, with significant remodeling of the extracellular matrix and collagen and fibronectin deposition. Interestingly, there is no evidence of net growth of the vascular wall (which results in so-called eutrophic remodeling), particularly in the milder forms of human essential hypertension. Hypertrophic remodeling and increased small artery stiffness may be found in more severe forms of hypertension. Almost all hypertensive patients have vascular structural remodeling. However, only some exhibit endothelial dysfunction. This is particularly true in mild hypertension, in which endothelial dysfunction is less common. A 1-year treatment of hypertensive patients with angiotensin converting enzyme inhibitors, angiotensin AT1 receptor antagonists, and long acting calcium channel blockers corrected small artery structure and, to variable degrees depending on the agents used, impaired endothelial function. In contrast, beta blockers did not improve structure, function, or mechanics of vessels. When beta-blocker-treated patients were switched to an AT1 receptor antagonist, small artery structure and impaired endothelial function were corrected. The vascular protective action of some antihypertensive agents may contribute to improve outcome for hypertensive patients, although this is presently unproven.
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PMID:Effect of antihypertensive treatment on small artery remodeling in hypertension. 1271 May 31