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)

This study was conducted to evaluate the effects of an SH-radical in an angiotensin converting enzyme (ACE) inhibitor on PGI2 generation, intracellular cGMP, and Ca2+ kinetics in vascular endothelial cells. In the cultured human umbilical vein endothelial cells, the non-SH containing ACE inhibitors, delapril and enalapril, did not result in significant changes in cGMP concentrations. By comparison, captopril significantly (P less than .01) increased cGMP concentrations. Only captopril showed a significant (P less than .01) effect on 45Ca kinetics in cultured human vascular endothelial cells. Captopril also decreased PGI2 generation in vascular endothelial cells. These effects were not seen with delapril or enalapril. The significance of the SH moiety in ACE inhibitors remains controversial. However, these results suggest that there could be differences in the vascular actions of ACE inhibitors related to the presence or absence of SH radical.
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PMID:Comparative studies of angiotensin converting enzyme inhibitors with and without the SH-radical. 184 88

Prostaglandins (PG) play an important role in the regulation of the renal blood flow and glomerular filtration rate. This study was designed to examine PG synthesis in the presence and absence of the ACE inhibitor captopril, PG binding to specific receptors and the ability of PG to stimulate cAMP accumulation in isolated glomeruli. Glomeruli were isolated from rat kidneys by a passive mechanical sieving technique. PG synthesis was determined by RTLC and RIA. The main eicosanoids synthesized by glomeruli were PGF2 alpha, thromboxane (TX) A2 (measured as TXB2), PGI2 (measured as 6-keto-PGF1 alpha) and PGE2. Binding experiments were performed with PGE1, PGE2 and the PGI2 analogue iloprost. Scatchard analysis revealed that the specific binding was highest for PGE1, followed by iloprost and PGE2. Adenylate cyclase was preferentially stimulated by PGE1 and PGE2, and to a lesser extent by PGI2, whereas PGF2 alpha had almost no effect. Captopril reduced mainly TXB2 concentrations. Glomerular TXB2 reduction, therefore, seems to be an additional hypotensive effect of captopril medication.
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PMID:[Glomerular prostaglandins: synthesis, mechanism of action and interaction with ACE inhibitors]. 185 Sep 40

We present preliminary data of a study comparing captopril, a short acting, with lisinopril, a long acting ACE-inhibitor in 8 of 12 projected patients with severe chronic heart failure (NYHA III-IV) and one additional risk factor (e.g. diabetes mellitus, renal failure). The 8 patients were treated in a cross over design for 12 weeks with either drug. While lisinopril improved NYHA-class in all patients, captopril reached this goal in only 3. Renal function was stable in all patients. Captopril influenced hormones (renin, aldosterone, norepinephrine, epinephrine) and microalbuminuria less than lisinopril. The number of adverse reactions was smaller in lisinopril treated patients. These preliminary data demonstrate at least an equal efficacy of lisinopril compared to captopril in high risk patients with severe chronic heart failure.
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PMID:[Comparison of lisinopril and captopril in treatment of severe heart failure (NYHA III-IV) in high risk patients. Preliminary results of the trial]. 185 Sep 42

There is considerable evidence to suggest that isolated tissues have the capacity to generate angiotensin II and that angiotensin II thus generated may enhance noradrenergic neurotransmission. In the present study the possibility that there may be local formation of angiotensin II within the rat vena cava and its consequence to noradrenergic transmission has been investigated. The angiotensin II precursors, angiotensin I and a synthetic tetradecapeptide renin substrate, each enhanced the stimulation-induced efflux of radioactivity from tissues previously incubated with 3H-noradrenaline. The effects of angiotensin I were blocked by the converting enzyme inhibitor captopril and the receptor antagonist saralasin, indicating local conversion to angiotensin II. The effect of the tetradecapeptide was blocked by saralasin, but not by captopril, suggesting either a direct effect of this peptide or conversion to angiotensin II by a pathway not involving angiotensin converting enzyme. The beta-adrenoceptor agonist isoprenaline enhanced noradrenergic transmission in the rat vena cava, relaxed guinea-pig trachea precontracted with carbachol and increased heart rate in rat isolated atria. Captopril and saralasin blocked the effect of isoprenaline in the vena cava, but did not alter its effects in the atria or trachea. This suggests that in the rat vena cava the facilitation of noradrenergic transmission by isoprenaline may involve stimulation of local angiotensin II production.
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PMID:Angiotensin II generation in the rat vena cava: stimulation of local synthesis by beta-adrenoceptor activation. 185 41

Captopril ((2S)-1-(3-mercapto-2-methyl-propionyl)-L-proline) inhibited the bifunctional, Zn(2+)-containing enzyme leukotriene A4 hydrolase/aminopeptidase reversibly and competitively with Ki = 6.0 microM for leukotriene B4 formation and Ki = 60 nM for L-lysine-p-nitroanilide hydrolysis at pH 8. Inhibition was independent of pH between pH 7 and 8, the optimum range for each catalytic activity. Half-maximal inhibition of leukotriene B4 formation by intact erythrocytes and neutrophils required 50 and 88 microM captopril, respectively. In neutrophils and platelets neither 5(S)-hydroxyeicosatetraenoic acid, 12(S)-hydroxyeicosatetraenoic acid, nor leukotriene C4 formation were reduced, indicating selective inhibition of leukotriene A4 hydrolase/aminopeptidase, not 5-lipoxygenase, 12-lipoxygenase, or leukotriene C4 synthase. In whole blood, captopril inhibited leukotriene B4 formation with an accompanying redistribution of substrate toward formation of cysteinyl leukotrienes. The decrease in leukotriene B4 was more substantial than the corresponding increase in cysteinyl leukotrienes suggesting that nonenzymatic hydration predominates over transcellular metabolism of leukotriene A4 by platelets during selective inhibition of leukotriene A4 hydrolase. Enalapril dicarboxylic acid and Glu-Trp-Pro-Arg-ProGln-Ile-Pro-Pro which inhibit angiotensin-converting enzyme: angiotensin I, bradykinin, and N-[3-(2-furyl)acryloyl]Phe-Gly-Gly which are substrates; and chloride ions which activate angiotensin-converting enzyme did not modulate leukotriene A4 hydrolase/aminopeptidase activity. The results indicate that: (i) the sulfhydryl group of captopril is an important determinant for inhibition of leukotriene A4 hydrolase/aminopeptidase, probably by binding to an active site Zn2+; (ii) aminopeptidase and leukotriene A4 hydrolase display differential susceptibility to inhibition; (iii) there is minimal functional similarity between angiotensin-converting enzyme (peptidyl dipeptidase) and leukotriene A4 hydrolase/aminopeptidase; (iv) captopril may be a useful prototype to identify more potent and selective leukotriene A4 hydrolase inhibitors.
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PMID:Inhibition of leukotriene A4 hydrolase/aminopeptidase by captopril. 188 82

The angiotensin converting enzyme inhibitor captopril has been shown to cause resetting of the arterial baroreflex to a lower pressure without a change in gain. The present study was conducted to determine whether captopril altered the relationship between arterial pressure, heart rate, and renal sympathetic nerve activity in conscious quietly resting dogs. Fourteen instrumented dogs were given 2 mg/kg iv of captopril; 10 min later postcaptopril measurements were made. Six of the fourteen dogs were pretreated with cyclooxygenase inhibitor (indomethacin or meclofenamate) before administration of captopril. Renal nerve activity and hemodynamics were measured in a final group of eight dogs in which arterial pressure was lowered with a graded infusion of sodium nitroprusside. Captopril caused a small but significant decrease in arterial pressure. This decrease in arterial pressure was accompanied by a significant increase in heart rate; however, renal sympathetic nerve activity was significantly reduced. In contrast, dogs receiving nitroprusside exhibited an increase in both heart rate and renal sympathetic nerve activity in response to similar decreases in arterial pressure. Dogs that received cyclooxygenase inhibitor showed reduced arterial pressure in response to captopril, increased heart rate, and increased renal sympathetic nerve activity. This study is the first to report a decrease in sympathetic nerve activity in response to captopril in an awake chronically instrumented animals. These data suggest that captopril's ability to augment prostaglandin synthesis is responsible for the observed sympathoinhibition.
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PMID:Renal sympathetic nerve and hemodynamic responses to captopril in conscious dogs: role of prostaglandins. 189 41

Physical exercise can increase urinary albumin excretion rate (UAER) in diabetic patients without microalbuminuria at rest (stage II diabetic nephropathy) or with baseline microalbuminuria (stage III diabetic nephropathy). The aim of this study was to compare the acute effects of captopril, an ACE inhibitor, and nifedipine, a calcium channel blocker, on exercise-induced microalbuminuria in hypertensive insulin-dependent (Type I) and non-insulin-dependent (Type II) diabetic patients with early stage nephropathy. Non-obese diabetic patients, 13 Type I (7 with stage II and 6 with stage III nephropathy) and 14 Type II (6 with stage II and 8 with stage III nephropathy), with hypertension, WHO stages I-II, underwent five submaximal cycloergometric tests: the first two in basal conditions, the other three after 24 hour administration of captopril (25 mg twice daily), placebo (1 tab twice daily) or nifedipine AR (20 mg twice daily) according to a randomised, double-blind design. Acute administration of both captopril and nifedipine was able to reduce exercise-induced microalbuminuria in hypertensive Type I and Type II diabetic patients regardless of the stage of their nephropathy. Captopril reduced systolic blood pressure less than nifedipine, in both Type I and Type II diabetics, but was more effective than nifedipine in blunting exercise-induced microalbuminuria, especially in Type I diabetics.
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PMID:Albuminuria induced by exercise in hypertensive type I and type II diabetic patients: a randomised, double-blind study on the effects of acute administration of captopril and nifedipine. 192 Mar 40

Angiotensin converting enzyme inhibitor therapy decreases the production of the vasoconstrictive angiotensin II and reduces the degradation of certain kinines of vasodilatator action. Of captopril, enalapril, and lysinopril marketed abroad, only captopril of shorter action is available in Hungary. Angiotensin converting enzyme inhibitors are new means for the therapy of hypertension and congestive heart failure. Captopril seems to be effective at an early stage of heart failure. It slows down or even inhibits the progression of heart failure. New aspects of therapy have been revealed. It may be successfully used in angina pectoris, for the prevention of reperfusion arrhythmias accompanying myocardial infarction, for the treatment of renoparenchimal renal diseases, diabetic nephropathy. The side-effects, interactions, and dosage of angiotensin converting enzyme inhibitors have also been discussed.
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PMID:Angiotensin converting enzyme inhibitor therapy. 194 79

Dehydration can be brought about by either water deprivation or by heat exposure (thermal dehydration). Angiotensin II has been shown to have a role in water deprivation-induced thirst. The current study was designed to determine whether angiotensin II is involved in thirst caused by thermal dehydration. Male Sprague-Dawley strain rats were dehydrated by exposure to a 40 degree C environment for 2-4 h or by water deprivation for 44 h. Water deprivation but not heat exposure significantly increased plasma renin activity. Neither ureteric ligation nor nephrectomy significantly altered water intake after thermal dehydration. Captopril, an inhibitor of angiotensin converting enzyme, given at a dose of 100 mg/kg ip, significantly decreased water intake in water-deprived rats but not in thermally dehydrated rats. Angiotensin II therefore does not appear to play a role in the control of water intake of thermally dehydrated rats. The physiological responses to dehydration in rats are dependent on the way in which the dehydration is brought about.
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PMID:Thermal dehydration-induced thirst in rats: role of angiotensin II. 195 66

A rapid and highly efficient procedure for purification of kininase II from human seminal plasma is described. After ultracentrifugation, the enzyme was purified by gel filtration on Sepharose 6B CL and ion exchange chromatography followed by affinity chromatography of EDTA-inhibited enzyme on bradykinin-Sepharose. The enzyme was specifically inhibited by Captopril and BPP9a but not by phosphoamidon. PAGE in the presence of sodium dodecyl sulfate under reducing conditions resulted in two major protein bands with apparent molecular masses of about 55 kDa and 65 kDa and two faint protein bands at higher molecular masses. Antibodies raised against the major protein bands showed full cross reactivity with all four protein bands. The presented data indicate that kininase II of subunits.
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PMID:Proteins of the kallikrein-kinin system in human semen. Isolation and properties of kininase II. 196 11


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