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)

The effects of hydralazine (3 mg/kg) and the angiotensin I-converting enzyme (ACE) inhibitor captopril (SQ 14,225) (100 mg/kg) on mean arterial blood pressure, plasma renin activity, urinary volume and urinary Na+,K+, and aldosterone concentrations were examined in spontaneously hypertensive rats of the Okamoto and Aoki strain (SHR) after oral daily dosing for 2 weeks, 3 or 6 months. Captopril caused progressive cumulative reductions in blood pressure resulting in normalization of pressure after 6 months of dosing. Hydralazine also significantly reduced blood pressure but not to the level of normotensive rats of the Wistar-Kyoto strain (WKY). Reductions in heart size paralleled the changes in blood pressure, normalization of cardiac hypertrophy occurring after captopril but not hydralazine. Plasma renin activity increased approximately 2-3 fold after hydralazine and 15-fold after captopril. Neither hydralazine nor captopril had any consistent effects on 24-hr urine volume, urinary Na+,K+ or aldosterone excretion. These results indicate that chronic inhibition of ACE with captopril induces normalization of blood pressure in SHR, a normal-renin model of hypertension.
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PMID:Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats. 23

This study was designed to investigate the effects of antihypertensive drugs on vascular hypertrophy and vascular angiotensin II in vivo in spontaneously hypertensive rats (SHR). Hydralazine (10 mg/kg/day), delapril (angiotensin converting enzyme inhibitor; 20 mg/kg/day), manidipine (calcium channel blocker; 10 mg/kg/day), and vehicle were given by gavage to four groups of SHR between 4 and 5 months of age. The aortic angiotensin II level was measured by highly sensitive radioimmunoassay coupled with high pressure liquid chromatography; aortic morphologic studies were performed. Each drug treatment effectively lowered blood pressure to the same level. However, the aortic wall thickness, medial-intimal areas, and wall to lumen ratio of abdominal aorta decreased significantly (p < 0.05, p < 0.01, p < 0.01, respectively) with delapril and manidipine but not hydralazine. Delapril significantly decreased aortic angiotensin II levels (p < 0.05), whereas manidipine treatment significantly increased them (p < 0.05). The aortic angiotensin II level was not changed by hydralazine. These results show that delapril and manidipine caused regression of hypertension-induced vascular hypertrophy in SHR. The probable mechanism of regression of aortic hypertrophy by delapril was inhibition of vascular angiotensin II formation, but the mechanism for manidipine was unclear.
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PMID:Regression of hypertension-induced vascular hypertrophy by an ACE inhibitor and calcium antagonist in the spontaneously hypertensive rat. 134 88

Nitrate derivatives are venous vasodilators which are effective in reducing the symptoms of pulmonary congestion. The beneficial action on exercise capacity was recently demonstrated in the Veterans II Study in association with Hydralazine and has also been suggested by other trials. The reduction in mortality from cardiac failure was demonstrated in the Veterans I Study in association with Hydralazine compared to conventional digitalo-diuretic therapy but seems less important than that obtained by angiotensin converting enzyme inhibitors. The phenomenon of tolerance seems to be related to the use of high doses in continuous therapy and may be countered by discontinuous use of the drug during the 24 hour period. Tolerance seems to be related to neuro-hormonal factors and perhaps to depletion of SH groups. Simultaneous use of nitrates and ACE inhibitors seems to be an interesting therapeutic concept.
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PMID:[Nitrate derivatives and cardiac insufficiency]. 153 Apr 25

The goal of the present study was to compare the effects of cilazapril, a new long-acting angiotensin converting enzyme inhibitor, to those of captopril and hydralazine on the coronary vascular bed. For this purpose, spontaneously hypertensive rats were treated for 4 months with either placebo, 10 mg/kg/day cilazapril, 100 mg/kg/day captopril, or 10 mg/kg/day hydralazine. At the end of treatment, maximal coronary blood flow was measured during maximal coronary vasodilation with adenosine in isolated perfused hearts. Cilazapril was the most effective drug in increasing maximal coronary blood flow. Captopril was less effective in improving maximal coronary blood flow but was as effective as cilazapril in reducing cardiac hypertrophy. Hydralazine had an extremely small effect on cardiac hypertrophy and maximal coronary flow reserve. The ranking of efficacy was similar for the reduction of vessel wall hypertrophy in the coronary arteries and arterioles. Because of the higher efficacy of cilazapril compared with captopril, a second experiment was performed in which 10 mg/kg/day cilazapril was compared with 100 mg/kg/day captopril and 300 mg/kg/day captopril after 1 month of treatment. Captopril increased maximal coronary flow and decreased cardiac hypertrophy to the same level as cilazapril only at the highest dose. We conclude that angiotensin converting enzyme inhibitors, in contrast to hydralazine, can increase markedly maximal coronary flow in spontaneously hypertensive rats but that this increase does not always parallel the decrease of cardiac hypertrophy and is closely dose dependent.
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PMID:Effects of two angiotensin converting enzyme inhibitors and hydralazine on coronary circulation in hypertensive rats. 183 28

The function of the endothelium is impaired in hypertension. In spontaneously hypertensive rats (SHR), acetylcholine-induced relaxation is decreased and serotonin-induced constriction is increased. The goal of our study was to evaluate the effect of a long-term treatment with cilazapril, a new angiotensin converting enzyme inhibitor, or hydralazine, a vasodilator, on the endothelium-dependent responses in aorta of SHR. Wistar-Kyoto rats were used as normotensive reference. Isolated aortic rings with or without endothelium were suspended in organ chambers. The rings with intact endothelium were contracted with norepinephrine. Acetylcholine-induced relaxation was markedly enhanced by cilazapril treatment. The tension achieved at maximal relaxation was 8 +/- 4% of norepinephrine contraction in the cilazapril-treated SHR versus 55 +/- 5% in the untreated SHR (p less than 0.001). Hydralazine had no significant effect. The effect of serotonin was also markedly modified by cilazapril. In untreated SHR, serotonin induced the release of a vasoconstrictor substance by the endothelium as assessed by the ratio of maximal tension induced by serotonin in rings with endothelium over maximal tension in rings without endothelium, which was greater than 1. This ratio was reversed in cilazapril-treated SHR but not in hydralazine-treated SHR. Captopril had effects similar to cilazapril. Finally, evaluation of carotid arteries showed that cilazapril also prevented morphological changes of the intima in SHR (i.e., infiltration by mononuclear cells). We conclude that angiotensin converting enzyme inhibitors prevent the functional and morphological alterations in endothelium that are found in hypertension and speculate that this action might participate in their antihypertensive effect.
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PMID:Effects of angiotensin converting enzyme inhibitors and of hydralazine on endothelial function in hypertensive rats. 222 54

Before efficacy of therapy has been proven in large populations years or decades may pass. Meanwhile the medical profession has to rely on probabilities. This holds true regarding improvement of prognosis of CHF by ACE inhibition. While symptomatic improvement of CHF by addition of ACE-inhibition. While symptomatic improvement of CHF by addition of ACE-inhibitors has been demonstrated in numerous studies, improvement of prognosis has not yet been demonstrated entirely sufficiently. Only one trial has been published so far in a severely ill but not very exactly defined population (66). Animal studies and several small or interim published trials, however, show that the positive influence of ACE-inhibitors on CHF pathophysiology and symptomatology might favourable affect the prognosis as well. The SAVE trial and the SOLVD trial - both have randomized several thousand patients - will give answers concerning the influence of Captopril and Enalapril on prognosis of symptomatic as well as asymptomatic left ventricular dysfunction and on progression of left ventricular dilatation. The VHEFT II trial will compare the effect of ACE-inhibitors with the combination of ISDN and Hydralazine. Results will be available within the first few years of this decade.
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PMID:[Heart insufficiency and life expectancy--the role of ACE inhibitors]. 240 50

In recent years, vasodilator drugs are considered a standard therapy for patients with symptomatic heart failure. Isosorbide dinitrate, venodilator, shows a striking fall in cardiac filling pressure. Hydralazine, arterially active vasodilator, decreases afterload and increases cardiac output. The combined use of nitrates and hydralazine shows synergistic effect in increasing cardiac output, lowering cardiac filling pressure and improving exercise tolerance and life expectancy. Prazosin showed no favourable effect on survival in a V-HeFT trial. Although calcium antagonists have been expected to improve hemodynamics in the patients with heart failure, there have been no controlled large trial to prove that the hemodynamic effect is accompanied by any improvement in exercise tolerance or quality of life. At the present, it is considered to be reasonable to use nitrates and hydralazine combined with ACE inhibitors, in patients with chronic heart failure.
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PMID:[Vasodilator therapy in cardiac failure]. 810 Dec 37

The myocardium contains a fibrillar collagen matrix that consists primarily of type I and type III collagens. There is a marked alteration in the ratio and amount of collagen phenotypes in myocardial hypertrophy due to pressure overload. The purpose of the present study is (1) to study the effect of antihypertensive therapy on collagen phenotypes, if instituted before development of hypertension in spontaneously hypertensive rat (SHR), and continued into adult life and (2) to study the effects of dissociation of hypertension from hypertrophy, on collagen phenotypes in SHRs. The present study shows the effect of two antihypertensive drugs, hydralazine and captopril, on collagen phenotypes in SHRs. Both hydralazine and captopril effectively controlled blood pressure in SHRs, but only captopril regressed hypertrophy and corrected the altered distribution of myocardial collagen phenotypes I and III. Untreated SHRs had a collagen type I:III ratio of 10.19 +/- 0.27, compared with that of 6.41 +/- 0.30 in normotensive WKY (P < 0.001). Captopril-treated SHRs had a collagen type I:III ratio of 6.75 +/- 0.37, which did not differ significantly from that in normotensive WKY. Hydralazine-treated SHRs had a collagen I:III ratio of 10.07 +/- 0.39, which is similar to the ratio in untreated SHRs. In normotensive rats, neither captopril nor hydralazine significantly altered collagen content or the ratio of type I:III collagen. Thus captopril, an angiotensin converting enzyme inhibitor, not only regressed hypertrophy but also reversed the altered distribution of type I and type III collagen whereas hydralazine which effectively controlled blood pressure, did not regress hypertrophy and did not correct the altered distribution in collagen phenotypes. These studies suggest that alteration of collagen phenotypes during hypertensive hypertrophy is independent of blood pressure control and myocardial mass.
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PMID:Alteration of cardiac collagen phenotypes in hypertensive hypertrophy: role of blood pressure. 847 26

Possible involvement of cardiac renin-angiotensin system (RAS) in pressure overload induced left ventricular hypertrophy (LVH) was investigated. Rats were subjected to abdominal aortic constriction (AAC) and examined the effects of 4 weeks treatments with an angiotensin converting enzyme (ACE) inhibitor, captopril and a vasodilator, hydralazine on haemodynamics and ventricular RNA, DNA, protein and myosin isoform pattern in sham and hypertrophied rats. AAC increased the mean arterial pressure (MAP) and systolic blood pressure (SBP), and resulted in increased left ventricle/body weight ratio, LV thickness, RNA and protein content, however total DNA was not changed. The expression of fetal isogene, beta-myosin heavy chain (beta-MHC), was markedly enhanced where as alpha-MHC was reduced. High-dose captopril (100 mg/kg p.o.,) significantly prevented the increase in haemodynamics, development of LVH, LV remodeling, increase in total protein, RNA and antithetical expression of myosin isoforms. Hydralazine (15 mg/kg p.o.,), did not modulate hypertrophic changes and low-dose captopril (1.5 mg/kg p.o.,) which has not produced any marked fall in MAP and SBP also modulated favourably the development of LVH and its biochemical markers. Thus, the prevention of the development of LVH and induction of beta-MHC by non-hypotensive doses of captopril may be related to the blockade of intracardiac production of angiotensin II rather than circulating system. These results suggest that cardiac RAS may play an important role in pressure overload induced LVH.
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PMID:Role of cardiac renin-angiotensin system in the development of pressure-overload left ventricular hypertrophy in rats with abdominal aortic constriction. 871 33

Both hypertension and diabetes mellitus are multifaceted dynamic expressions of pathophysiological disequilibrium that are closely related with and even intermingled by a number of common factors. Hyperinsulinaemia and insulin resistance may be possible links between hypertension and diabetes mellitus. While working on the effect of different antihypertensive agents in several animal models of simultaneously occurring diabetes-mellitus and hypertension it was found that most antihypertensives prevented streptozotocin (STZ)-induced hypertension in rats. Hydralazine, angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers (CCB) and clonidine prevented STZ-induced cardiomyopathy, hyperlipidaemia and glucose tolerance. It was further demonstrated that atenolol produced many unfavourable effects like hyperlipidaemia and decreased cardiac functions. We also used other animal models of simultaneously occurring diabetes-mellitus and hypertension such as genetically hypertensive or spontaneously hypertensive (SH), Deoxycorticosterone acetate (DOCA)-hypertensive and neonatal streptozotocin-induced NIDDM rats. Results of our studies suggest that SH, neonatal STZ-induced NIDDM, and fructose hypertensive rat models may be considered as models for insulin resistance - the concept that has come into limelight in recent years. DOCA may have some influence on glucose homeostasis and insulin sensitivity and some sort of counteraction to STZ-induced cardiovascular and metabolic changes occur with DOCA. Hence, it may not be considered as an ideal model to study the metabolic and cardiovascular complications of hypertension associated with diabetes-mellitus. Among ACE inhibitors, perindopril, spirapril, and among calcium channel blockers (CCB) used in our study amlodipine and nifedipine were found to produce an increase in insulin sensitivity. Enalapril, ramipril, lisinopril and nitrendipine failed to alter insulin sensitivity as far as the glycaemic control is concerned. Extension of the results of these experiments to the clinical practice substantiated many of the findings and a good correlation between results obtained from experimental studies and clinical data was found.
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PMID:Hyperinsulinemia and insulin resistance in hypertension: differential effects of antihypertensive agents. 1005 52


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