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)

Enalapril is a new, oral, long-acting nonsulfhydral angiotensin converting enzyme inhibitor. Thirty-nine patients with primary hypertension were entered into a randomized, double-blind protocol to assess the efficacy of enalapril (10 to 20 mg bid), hydrochlorothiazide (25 to 50 mg bid), or combined drug therapy. Enalapril, either alone or in combination with hydrochlorothiazide, effectively controlled blood pressure. Enalapril monotherapy was associated with an increase in plasma renin activity and a decrease in angiotensin II concentration; in patients with an initial inulin clearance less than or equal to 80 mL/min/1.73 m2, inulin and para-aminohippurate clearances were markedly improved, without producing adverse effects on salt and water excretion or body fluid composition. Combination therapy was associated with a marked increase in plasma renin activity; however, only those patients with an initial inulin clearance less than or equal to 80 mL/min/1.73 m2 demonstrated suppression of angiotensin II concentration and marked improvement in inulin and para-aminohippurate clearances. These observations suggest that enalapril, either alone or in combination with a diuretic, has the potential to reverse renal function abnormalities encountered in the hypertensive state.
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PMID:Effects of enalapril alone, and in combination with hydrochlorothiazide, on renin-angiotensin-aldosterone, renal function, salt and water excretion, and body fluid composition. 299 32

In 40 to 50 percent of the essential hypertensive population, a high intake of sodium does not increase renal blood flow. These patients have been called "non-modulators" since their adrenal and renal vascular responses to angiotensin II are not modified by changes in sodium intake. To determine if these patients form a distinct subgroup, the frequency distribution of four characteristics that have been reported to be abnormal in non-modulators were analyzed: aldosterone secretory response to acute volume depletion, plasma aldosterone response to angiotensin II infusion, plasma renin activity response to saline infusion, and renal blood flow response to salt loading. All four characteristics had a bimodal distribution in patients with hypertension. The effect of angiotensin converting enzyme inhibition on two of these abnormalities was also reviewed. In both cases--aldosterone secretory response to angiotensin II and renal blood flow response to salt loading--converting enzyme inhibition restored the abnormal responses towards normal values in non-modulators without altering the responses in normotensives or modulators. Indeed, the correction of the abnormal renal blood flow response to salt loading through converting enzyme inhibition may explain how converting enzyme inhibitors normalize blood pressure in 50 percent of the patients in whom the renin-angiotensin system is suppressed by an unrestricted, typically high, intake of salt. In summary, non-modulators are a distinct subset of the hypertensive population. Converting enzyme inhibition corrects the abnormalities that may be responsible for their hypertensive condition and, therefore, may be a specific form of therapy for these patients.
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PMID:Are non-modulating patients with essential hypertension a distinct subgroup? Implications for therapy. 299 43

Antihypertensive activity of alacepril (1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine, DU-1219), an orally active angiotensin converting enzyme (ACE) inhibitor, was investigated in hypertensive models with normal or low plasma renin activity (PRA). After single oral administration in spontaneously hypertensive rats (SHR), alacepril (1-30 mg/kg) showed a dose related antihypertensive effect with a gradual onset and long lasting action. The maximum hypotensive effect was about 3 times more potent than that of captopril (3-100 mg/kg) on a weight basis. When comparing the AOC (area over the antihypertensive curve) values, the overall antihypertensive activity of alacepril was 8 times stronger than that of captopril. In deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats, alacepril (10-100 mg/kg) produced a significant and sustained hypotensive effect. The maximum hypotensive potency and the overall antihypertensive activity of alacepril were remarkably stronger than those of captopril (30, 100 mg/kg). During once daily successive oral administration for 10 days in SHR, alacepril (3-10 mg/kg/d) reduced dose relatedly the daily starting blood pressure. In DOCA-salt hypertensive rats and dogs, alacepril (30 mg/kg/d) produced a significant antihypertensive effect, while captopril (30 mg/kg/d) did not reduce daily starting blood pressure. Therefore, it may be expected that alacepril is a more effective antihypertensive agent than captopril in various hypertensions of different etiology.
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PMID:Antihypertensive activity of alacepril in spontaneously hypertensive rats and deoxycorticosterone acetate-salt hypertensive rats and dogs. 300 Mar 90

Angiotensin converting-enzyme inhibitors cross the placenta and modify the maternal, foetal and utero-placental renin-angiotensin system. Eight cases of pregnancy in women taking captopril have been published, 7 other cases being reported in this review paper. There were one spontaneous and 2 therapeutic abortions, one of which disclosed a malformation of uncertain diagnosis and imputation. One intrauterine death at 28 weeks was probably due to the severity of the maternal disease. Two children born to mothers also treated with frusemide died of neonatal anuria. Delivery or caesarean section occurred before term in 8 cases, and there were 3 cases of neonatal respiratory distress with a favourable outcome. Finally, one mother gave birth at term to twins of normal weight. The cases with respiratory distress can be attributed to the mother's hypertension, to prematurity and/or to concomitant treatment with beta-blockers, while the cases with anuria seem to be due to inhibition of the effects of angiotensin on renal haemodynamics, with salt depression as a possible aggravating factor. Treatment with angiotensin converting enzyme inhibitors does not seem to warrant therapeutic abortion. However, these drugs are contra-indicated in pregnancy and should only be given to women wishing to become pregnant if they present with resistant and dangerous arterial hypertension. A programme of pharmacovigilance is being set up to follow up such pregnancies.
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PMID:[Inhibition of angiotensin converting enzyme in human pregnancy. 15 cases]. 300 90

Aldosterone suppression is said to play a major role in the long term hypotensive efficacy of angiotensin converting enzyme inhibitors. However, in previous reports from other laboratories, plasma volume has been found mostly increased and sodium balance sometimes positive. The effects of the angiotensin converting enzyme inhibitor enalapril (10-40 mg/day, p.o., for 6 weeks) on blood pressure, body fluid volumes, renal function and plasma aldosterone were compared to those of hydrochlorothiazide (50 mg/day, p.o.) alone for 2 weeks and in association with propranolol (80-160 mg/day, p.o.) for 4 more weeks during a randomized double-blind parallel study in 14 essential hypertensives. Hydrochlorothiazide alone and in combination with propranolol induced slight and not significant change in either blood pressure and body fluids. The maximum hypotensive response to enalapril was achieved only after 2 weeks of continuous treatment possibly because after 1 week the hypotensive efficacy was lessened by a significant (P less than 0.05) fluid retention secondary to a transient and not significant fall in renal perfusion. At this time aldosterone was not significantly changed compared to pretreatment values. After 6 weeks on enalapril, blood pressure was significantly reduced, plasma aldosterone further but not significantly decreased and extracellular fluid volume was normal. These findings indicate that aldosterone suppression contributes to the blood pressure lowering effect of enalapril by offsetting the salt and water retention observed on starting treatment and due to direct vasodilation.
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PMID:Time course of changes in blood pressure, aldosterone and body fluids during enalapril treatment: a double-blind randomized study vs hydrochlorothiazide plus propranolol in essential hypertension. 301 29

We have studied the degradation of bradykinin, lysyl bradykinin and des-Arg9-bradykinin by the angiotensin converting enzyme. Bradykinin was cleaved at two sites to produce the pentapeptide Arg-Pro-Pro-Gly-Phe plus dipeptides Ser-Pro and Phe-Arg. Lysyl bradykinin was cleaved similarly to release the same dipeptides plus the hexapeptide Lys-Arg-Pro-Pro-Gly-Phe. The tripeptidase activity of ACE was observed when des-Arg9-bradykinin was digested. A single cleavage yielded the above pentapeptide plus Ser-Pro-Phe. Although des-Arg9-bradykinin was the most rapidly digested, when mixtures of des-Arg9-bradykinin and bradykinin or lysyl bradykinin were tested, virtually all of the bradykinin and most of the lysyl bradykinin was digested prior to the onset of digestion of des-Arg9-bradykinin. This was shown to be due to inhibition of des-Arg9-bradykinin cleavage by kinins and kinin-degradation products. The order in terms of potency was bradykinin greater than lysyl bradykinin greater than Ser-Pro much greater than Phe-Arg greater than Arg-Pro-Pro-Gly-Phe. The concentration of chloride ion was an important parameter which affected the rate of digestion of each substrate examined. des-Arg9-bradykinin was not digested by ACE in the absence of sodium chloride and the rate of digestion increased as the chloride concentration was increased to 100-150 mM. On the other hand, increasing NaCl concentration was inhibitory for bradykinin digestion. The rate of Lys-bradykinin digestion was increased from 0 to 1 mM NaCl and decreased thereafter up to physiologic concentration. A half-maximal rate was seen at 100-150 mM NaCl compared to no salt. Of the divalent cations examined, cupric ion inhibited further digestion of des-Arg9-bradykinin at physiologic concentrations. Our data indicate that the rate of degradation of kinins and the nature of the stable final cleavage products in plasma or serum (studied in vitro) are dependent upon the effects of chloride ion, metal ions, and the kinetic effects of multiple metabolites produced by at least two kininases.
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PMID:Studies of the digestion of bradykinin, Lys-bradykinin, and des-Arg9-bradykinin by angiotensin converting enzyme. 301 4

CHF may activate the RAS by various mechanisms. Acute CHF is associated with high PRA, whereas chronic, stable disease is combined with normal values. The response to ACEI is affected by blood pressure, degree of activation of the RAS, salt balance and degree of possible renal failure. It may also be affected by concomitant diuretic or, e.g., digoxin therapy. ACEI improves RPF, GFR may remain normal or may increase, if it was previously impaired due to reduced RPF. Severe hypotension in combination with decreased autoregulatory capacity may decrease GFR. Generally, renal excretion of sodium and water increase. These changes in renal handling of salt and water are primarily caused by decreased AII. They are also augmented by inhibited sympathetic tone and thirst and decreased release of ADH and aldosterone. Increased synthesis of vasodilating and natriuretic PGs is probably also of some importance. Dilutional hyponatremia may be corrected by combined ACE inhibitor and furosemide treatment. Water and sodium excretion increase and sodium is redistributed from the intracellular space. Low serum sodium values increase and azotemia may be corrected, if ACE inhibitor doses are carefully titrated to avoid severe hypotension. These effects are ascribed mainly to a decrease of AII, thirst and ADH release. The effect of furosemide is improved since increased amounts of salt are delivered to the loop of Henle and access of furosemide to its site of action is facilitated by increased RPF. ACEI does not cause any obvious negative effects on renal handling of salt and water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ACE inhibition on renal regulation of salt and water. 301 59

Possible non-renin antihypertensive actions of two angiotensin-converting enzyme inhibitors, the sulfhydryl compound captopril and the new nonsulfhydryl inhibitor quinapril (CI-906), were compared in rats with one-kidney deoxycorticosterone-salt hypertension. Plasma renin activity remained low during the 12-day treatments and showed very strong suppression of the renin-angiotensin system. Quinapril did not influence the rapidly increasing blood pressure. Although captopril tended to reduce the development of hypertension (p = 0.08), it did not have any significant effect, either. The results indicate that these ACE inhibitors with different chemical structures lack any significant blood pressure lowering mechanism in severe deoxycorticosterone-salt hypertension, a model in which they cannot act through their established antihypertensive mechanism, the inhibition of the renin-angiotensin system.
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PMID:Effects of two structurally different angiotensin-converting enzyme inhibitors, captopril and quinapril (CI-906), in rats with one-kidney deoxycorticosterone-salt hypertension. 302 83

In chronic congestive heart failure, there is stimulation of the renin-angiotensin-aldosterone system, in addition to other homeostatic mechanisms. In addition to increased tone in the arteriolar and venous beds, there is salt and water retention by the kidney and excitation of the central nervous system by angiotensin. Interference with the generation of angiotensin reduces preload and afterload without a reflex tachycardia as the effects of angiotensin on the central nervous system are reduced. ACE inhibition is, therefore, a logical approach to the management of chronic congestive heart failure.
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PMID:Why are the angiotensin converting enzyme inhibitors rational in the treatment of congestive heart failure? 302 14

This review focuses on the renal effects of the angiotensin converting enzyme inhibitors, captopril and enalapril. Emphasis is placed on the renal response to these drugs in patients with primary essential hypertension, and in hypertension accompanying renal parenchymal disease. Specifically reviewed are the renal function and hemodynamic, salt and water, body fluid composition, and urinary protein excretion responses. The interruption of the renin-angiotensin-aldosterone axis has the potential to produce a variety of favorable renal responses, including reduction of renal vascular resistance, enhancement of renal blood flow, enhancement of glomerular filtration rate, acute natriuresis, sustained diuresis, and a decrease in urinary protein excretion. Data in support of these potential renal perturbations are presented and discussed. The results suggest that the angiotensin converting enzyme inhibitors are important therapeutic agents in the treatment of hypertensive disease, in that they may modify pathophysiologic renal abnormalities encountered in this disease state.
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PMID:Renal effects of angiotensin converting enzyme inhibitors in hypertension. 302 81


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