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 mechanisms by which captopril inhibits vasopressin-stimulated osmotic water flow in the toad bladder have been investigated in vitro. Captopril has two possible mechanisms for the inhibitory action on the water flow, one is its stimulative effect on prostaglandin E2 (PGE2) biosynthesis by inhibition of kininase II activity, the other, is a direct effect on water flow independent of PGE2. Captopril inhibited the vasopressin-, cyclic adenosine monophosphate- and 3-isobutyl-1-methyl-xanthine-stimulated water flow. The inhibition of water flow by bradykinin was enhanced by captopril. These data indicate that captopril increased the amount of bradykinin in toad bladder cells resulting in the production of PGE2 which inhibited the increase in water flow induced by vasopressin. The inhibitory effect of captopril, however, also occurred in the presence of indomethacin, when the production of PGE2 was attenuated. Thus, it was concluded that captopril inhibits the vasopressin-stimulated water flow indirectly by inhibiting the degradation of bradykinin and thereby enhancing the production of PGE2, and directly at a site following the production of cyclic adenosine monophosphate by vasopressin.
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PMID:Mechanisms for the inhibition of vasopressin-stimulated water flow by captopril in the toad bladder. 244 80

The new angiotensin converting enzyme inhibitor, spirapril, was found to inhibit the pressor effects of angiotensin I about 10 times more potently than captopril in conscious rabbits. Its effects on systemic hemodynamics and regional blood flows were studied in two groups of 8 normotensive anaesthetized rabbits pretreated 24 h before the acute experiment either by substituting 0.45% NaCl for drinking water or with a subcutaneous injection of 20 mg kg-1 furosemide. Under barbiturate anaesthesia, regional blood flows were then measured with microspheres before and after i.v. administration of two doses of spirapril. With anaesthesia and surgery, plasma renin activity (PRA) was elevated in the salt-replete group and very high in the salt-depleted group (37 and 152 ng ml-1 h-1, respectively). Spirapril lowered blood pressure more in salt-depleted animals and increased only cardiac output and renal blood flow in salt-replete ones. Weak cardiodepression, associated with a small fall of cardiac output, was found in salt-depleted rabbits, indicating that very high angiotensin II levels may contribute to maintain cardiac function in volume-depleted animals with an activated sympathetic system. Coronary and skin blood flow decreased, and pancreatic and hepatic artery flow increased only in this group. A change in the salt balance can thus cause major differences in the responses of the peripheral circulation to angiotensin converting enzyme inhibition.
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PMID:Hemodynamic effects of a new angiotensin converting enzyme inhibitor, spirapril, in sodium-loaded and sodium-depleted rabbits. 244 12

Vasodilating drugs such as angiotensin converting enzyme (ACE) inhibitors may extend life expectancy in patients with congestive heart failure (CHF). The purpose of this study was to evaluate whether long-term therapy (365 days) with enalapril (ENAL, an ACE inhibitor), would prolong life in rats with a healed myocardial infarction (MI), an experimental model with hemodynamic characteristics of CHF. Seven days after sham or coronary ligation, when the healing phase of MI was well underway, 132 rats (75 sham, 57 MI) were randomized to receive either enalapril in the drinking water (17-25 mg/L, approximately 1.0 mg/kg/day) or tap water. The date of spontaneous death was recorded, and heart weight and MI size (by planimetry) were determined. Serum ENAL, total ACE concentration, and angiotensin and methoxamine pressor responses were quantified in 12 survivors. Long-term enalapril prolonged survival (p = 0.014) with a median 50% survival of 164 (164-165) days, compared to 84 (64-104) days in rats receiving tap water. There were twice as many MI rats alive at the end of one year on angiotensin converting enzyme inhibition (ACEI) therapy as compared to the untreated group. The average MI size (39-40%) was not different between groups, and there was a significant inverse correlation between date of death and MI size (r = 0.7-0.8) in both treatment groups. Cardiac hypertrophy was evident in all MI rats. Serum ENAL levels, after one year, were at the clinically relevant concentration (2.3 ng/ml) and total serum ACE (inhibitor removed) doubled to 4,300 nmol/h/ml.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased survival in rats with congestive heart failure treated with enalapril. 245 Feb 32

Cilazapril is a new inhibitor of angiotensin converting enzyme which has been shown to prevent development of high blood pressure and cardiac hypertrophy in spontaneously hypertensive (SHR) rats. The goal of the present experiment was to evaluate the effects of a chronic treatment with cilazapril on the decrease of coronary reserve in SHR rats. For this purpose, a group of 10 SHR rats which received by oral gavage 10 mg/kg/day of cilazapril for 9 weeks was compared with a control group of 9 SHR rats which received distilled water. Coronary reserve was evaluated by measuring coronary blood flow with the radioactive microspheres method before and after a dose of dipyridamole (2 mg/kg/min) which induces maximal coronary vasodilation. The left ventricular weight/body weight ratio was decreased in the cilazapril group compared to the placebo-treated group (p less than 0.001). Moreover, minimal coronary vascular resistance of the left ventricle and the right ventricle were 33% and 39%, respectively, lower in the cilazapril group as compared with the control group (p less than 0.01). We conclude that chronic treatment with cilazapril can prevent the development of left ventricular hypertrophy and the decrease of coronary vascular reserve in the left and right ventricles of spontaneously hypertensive rats.
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PMID:Cilazapril prevents the development of cardiac hypertrophy and the decrease of coronary vascular reserve in spontaneously hypertensive rats. 245 43

The therapeutic inhibition of angiotensin converting enzyme (ACE) is associated with the production of a dry cough, which occurs more commonly in women than men and appears to be unrelated to concurrent illness. At present the exact incidence of ACE inhibitor cough and the substrate of ACE responsible for this effect is unknown. Cough challenge by inhalation of aerosols of tussive agents such as citric acid and capsaicin may be used to study the effect of drug administration on the cough reflex. In normal subjects, an oral dose of captopril (25 mg) causes a significant shift in the dose-response curve to capsaicin inhalation, but not that to distilled water or citric acid. The exacerbation of artificially induced cough by ACE inhibition may be the result of a local increase in perineuronal substance P or bradykinin concentrations within the lung.
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PMID:Cough associated with angiotensin converting enzyme inhibition. 247 6

1. In a fourway double-blind placebo controlled study, the effects of cilazapril, a new angiotensin converting enzyme inhibitor, on renal function and the responses to intravenous frusemide were studied in a group of twelve salt depleted male volunteers. 2. Cilazapril produced an increase in effective renal plasma flow and urinary output of prostaglandin E2 metabolite (PGE2-M) but no effect on sodium, potassium or water excretion. 3. Pretreatment with cilazapril antagonised the effects of frusemide on glomerular filtration, PGE2-M and sodium excretion.
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PMID:The effects of cilazapril alone and in combination with frusemide in healthy subjects. 252 36

1. Streptozotocin diabetes was induced in Wistar-Kyoto rats fed a 50% protein diet. Animals were randomized to receive either the ACE inhibitor ramipril, 1 mg/L in drinking water (n = 7), or no treatment (n = 7) and were studied for 6 months. Blood glucose, body weight and glomerular filtration rate (GFR) were measured at 0, 1, 4, 8 and 16 weeks of diabetes and urinary albumin excretion was measured every 8 weeks. 2. In both groups, GFR increased significantly within 1 week of induction of diabetes (P less than 0.001) and thereafter remained stable. There was no difference in GFR between the treated and untreated groups. 3. Urinary albumin excretion increased progressively in both groups throughout the study. Ramipril treatment reduced albuminuria by approximately 50% at weeks 16 and 24 (P less than 0.01). 4. The amelioration of diabetic albuminuria by ACE inhibition, in the setting of high dietary protein intake, may have important implications for the treatment of human diabetic nephropathy.
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PMID:Ramipril reduces albuminuria in diabetic rats fed a high protein diet. 252 67

Serial determinations of protein excretion rate and systolic blood pressure (SBP) were made in spontaneously hypertensive rats (SHR) uninephrectomized (UNX) at six weeks of age and given tap water (CON), or water with hydrochlorthiazide, hydralazine and reserpine (HHR), captopril (CAP) or enalapril (ENP). Compared to CON, significant hypertension was prevented, kidney weight was lower and there was less proteinuria in HHR, CAP and ENP rats followed for 30 weeks after UNX. Morphologic studies of these four groups revealed that antihypertensive therapy reduced the incidence of glomerular sclerosis in UNX SHR by 50%. Despite complete absence of systemic hypertension, there was striking medial thickening of lobular arteries and arterioles of rats given the angiotensin converting enzyme (ACE) inhibitor, captopril. These vascular abnormalities were present to a lesser degree in rats given ENP, but were entirely absent in untreated animals or in those ingesting the HHR combination. Micropuncture studies performed five weeks after UNX in four additional groups of CON, HHR, CAP and ENP rats revealed that glomerular capillary pressure was elevated in CON and reduced by all three drug regimens. These studies support the hypothesis that glomerular capillary hypertension and/or nephron hypertrophy predispose to glomerular injury in this model of hypertension and reduced renal mass. ACE inhibitors and HHR are equivalent in their ability to prevent glomerular hypertension and damage in these rats, but the former, and in particular captopril, produce abnormalities of cortical vessels via a mechanism not dependent on the presence of systemic hypertension.
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PMID:Renal vascular effects of antihypertensive therapy in uninephrectomized SHR. 254 Mar 76

This study has evaluated the effects of the angiotensin converting enzyme inhibitor Enalapril on glomerular ultrastructure and albuminuria in normotensive and hypertensive diabetic rats. Streptozotocin-diabetes was induced in Wistar Kyoto and spontaneously hypertensive rats. Enalapril was administered in drinking water in diabetic normotensive, control hypertensive and diabetic hypertensive rats. Enalapril therapy prevented an increase in glomerular basement membrane thickness in diabetic normotensive, control hypertensive and diabetic hypertensive rats without any significant effect on fractional mesangial volume. Enalapril decreased albuminuria in diabetic normotensive, control hypertensive and diabetic hypertensive rats. Thus, enalapril retards the development of glomerular basement membrane thickening and albuminuria in the rat, in the presence or absence of hypertension.
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PMID:Enalapril retards glomerular basement membrane thickening and albuminuria in the diabetic rat. 255 9

Comparative effects of the angiotensin converting enzyme inhibitors captopril and enalapril on progression of chronic renal disease was studied in 3/4 nephrectomized rats. Rats were divided into sham and nephrectomized groups, and treated with plain water or water containing captopril (150 mg/liter) or enalapril (50 mg/liter). Evaluations were made 4 weeks before and 0, 4, 8, and 10 weeks after nephrectomy. Endogenous creatinine clearance decreased in drug-treated, nephrectomized rats to values less than sham controls, but remained greater than water-treated rats. Significant (P less than 0.05) proteinuria developed 4 weeks post-nephrectomy in water-treated rats, 8 weeks post-nephrectomy in captopril-treated rats, but did not develop in enalapril treated rats. Regression analysis of carbamylated plasma protein values vs plasma creatinine revealed significant (P less than 0.05) relationships only in the water-treated, nephrectomized rats from weeks 0 through 8, but were otherwise unaffected by treatment. Both drugs resulted in significantly (P less than 0.05) improved scores for renal histologic lesions as compared to water treatment. Modifications of proteinuria in captopril and enalapril-treated rats occurred prior to onset of changes in systolic blood pressure, which was significantly elevated only in water-treated, nephrectomized rats at weeks 8 and 10. We conclude that angiotensin converting enzyme inhibitors may ameliorate progression of experimental renal disease through intrarenal effects, independent of modulation of systemic blood pressure, and that enalapril may be superior to captopril in some regards.
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PMID:Comparative effects of captopril and enalapril on the progression of chronic renal disease in partially nephrectomized rats. 255 51


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