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 in vivo metabolism of atrial natriuretic peptide (ANP) has been studied in the rat after i.v. administration of either [106Phe-14C]- or [126Tyr-125I]-ANP(103-126). Plasma samples containing radioactive peptides were separated by reverse-phase high-performance liquid chromatography. The major plasma metabolites were [125I]Tyr and [14C]Phe for the iodinated and 14C-labeled peptides, respectively. Both peptides had ANP(104/5-126) as a metabolite. Administration of labeled peptide by either bolus or infusion produced the same metabolite profile. To determine which enzymes were responsible for generating these initial metabolites, animals were first dosed with various protease inhibitors before the infusion of [14C]ANP(103-126). The amino-peptidase inhibitor bestatin and the angiotensin converting enzyme inhibitor captopril caused 54 and 66% increases in plasma ANP(103-126), respectively, but no other effects. Administration of the endopeptidase 24.11 inhibitor thiorphan led to a 158% increase of ANP(103-126) in plasma and an 11-fold increase in ANP(104/5-126). The latter metabolite could be selectively decreased by pretreatment with bestatin in combination with thiorphan. The results demonstrate that the initial plasma metabolites of ANP(103-126) are due to the activity of endopeptidase 24.11, a bestatin-sensitive aminopeptidase, and a carboxypeptidase. The plasma clearance of the peptide is probably also due to cellular binding and uptake in combination with glomerular filtration as very few plasma metabolites were observed even at very high rates of ANP(103-126) infusion.
 ...
PMID:In vivo metabolism of atrial natriuretic peptide: identification of plasma metabolites and enzymes responsible for their generation. 252 86

1. The effect of acute angiotensin converting enzyme (ACE) inhibition on the plasma concentrations of atrial natriuretic peptide (ANP) was investigated in a single-blind placebo controlled crossover study in healthy volunteers. 2. Intravenous infusion of 2 mg cilazaprilat resulted in a significant and short lasting inhibition of ACE as evidenced by a decrease of plasma angiotensin II and an increase in plasma renin activity. 3. When compared with placebo cilazaprilat lowered diastolic pressure and increased heart rate significantly. 4. No effect of cilazaprilat was found on plasma ANP levels, suggesting that angiotensin II does not mediate ANP release.
 ...
PMID:The effect of acute ACE inhibition on atrial natriuretic peptide. 252 37

1. To determine the response of plasma atrial natriuretic peptide (ANP) to treatment with an angiotensin converting enzyme (ACE) inhibitor in heart failure, seven patients (NYHA Functional Class III-IV) were studied before and after the addition of ramipril to maintenance digoxin and diuretic treatment. 2. Baseline arterial ANP levels were raised, but fell during ramipril treatment in parallel with changes in both haemodynamic recordings (arterial pressure, pulmonary artery diastolic pressure, and right atrial pressure) and hormone levels (angiotensin II and aldosterone). 3. Coronary sinus ANP, measured in three patients, was greater than concomitant arterial levels, and the coronary sinus ANP secretion rate was calculated to be between 15 and 119 pmol/min. 4. These results demonstrate that improvement in haemodynamic function during ACE inhibitor treatment is associated with a decline in elevated ANP levels, and support the concept that atrial stretch or pressure regulates the secretion of atrial peptides in man.
 ...
PMID:Atrial natriuretic peptide levels in congestive heart failure in man before and during converting enzyme inhibition. 252 56

It has been suggested that angiotensin converting enzyme (ACE) may play a role in the metabolism of atrial natriuretic peptide (ANP), and that ANP may interfere with angiotensin-induced vasoconstriction. This has been investigated within the forearm vascular bed during local ANP infusion and ACE inhibition. Six normotensive volunteers were studied, each on two occasions. On both occasions, after saline infusion, volunteers were given initially a 20 min infusion of ANP at 0.1 microgram/min via the brachial artery. This was followed, after 20 min, by a second infusion of ANP at the same dose, co-infused with enalaprilat (5 micrograms/min) on one occasion, and placebo (saline) on the other (in random order). Forearm blood flow was measured using venous occlusion plethysmography with mercury-in-silastic strain gauges. Blood flow in the cannulated arm increased significantly during the first ANP infusion; by 52 +/- 15% before placebo (P less than 0.05), and by 41 +/- 8% before enalaprilat (P less than 0.005). This increase was similar with the second ANP infusion during co-infusion of either placebo (40 +/- 10%) or enalaprilat (45 +/- 11%). Enalaprilat did not affect the half-life of vasodilatation produced by ANP (t1/2 = 5 min). These studies in healthy subjects demonstrate no effect of local ACE inhibition on resting blood flow, or on the vasodilatation produced by ANP in the human forearm, and provide no evidence of a role of ACE in the metabolism of ANP in this vascular bed.
 ...
PMID:The effect of local angiotensin converting enzyme inhibition on the action of atrial natriuretic peptide in the human forearm. 254 49

The two major causes of death in congestive heart failure (CHF) are progressive heart failure (approximately 60% of cases) and sudden death (30%). Sudden death in CHF is caused primarily by malignant ventricular arrhythmias. The underlying mechanism has yet to be established, but myocardial metabolic factors are probably involved. Although there is a clear association between complex ventricular arrhythmias and left ventricular function, it has not been shown convincingly that antiarrhythmic agents can reduce sudden death in CHF. Progressive deterioration of myocardial function is associated with altered myocardial energy production. Notably, the physiological effects of neuroendocrine activation in chronic CHF may be deleterious to myocardial function. The CONSENSUS study was carried out to evaluate the association between neuroendocrine activation and deterioration of myocardial function using ACE inhibitors. A marked reduction in mortality rate occurred in the enalapril-treated group, where the one-year mortality was reduced by 31%. The reduction in mortality was solely among patients with progressive CHF (a reduction of 50%); there was no difference in the incidence of sudden death. Analysis of blood samples drawn at baseline in the placebo group showed a significant positive correlation between mortality and plasma angiotensin II (P less than 0.05), aldosterone (P = 0.003), noradrenaline (P less than 0.001), adrenal levels (P less than 0.001), and atrial natriuretic peptide (P = 0.003). This was not observed in enalapril-treated patients. The significant reduction in mortality in the enalapril group was found consistently among patients with baseline hormone levels above the median value. In CHF, the underlying disease may induce serious arrhythmias and/or progressive failure.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Mechanisms for improved survival in heart failure. 255 Jun 46

The haemodynamic and hormonal effects of an elective change of antihypertensive therapy from a beta-adrenoceptor blocking drug to a converting enzyme inhibitor, enalapril, were monitored in 12 hypertensive in-patients (WHO I). Blood pressure and heart rate were determined every 2-4 h using an automatic sphygmomanometer during an abrupt cessation of the previous beta-adrenoceptor blocking drug and commencement of treatment with enalapril 20 mg o.d. 12 h later. Mean blood pressure values at rest and during the hand grip test were lower when on enalapril, but heart rate was significantly higher, and three patients suffered from palpitations during the change. The change resulted in an improvement in cardiac function both at rest and during isometric work, as shown by echocardiography. A rapid decrease in plasma angiotensin converting enzyme (ACE) activity and an increase in renin activity were also seen after the change, while plasma levels of atrial natriuretic peptide (ANP) decreased towards normal values. The results suggest that an abrupt change from a chronic beta-adrenoceptor blocking drug to enalapril is safe, feasible and is likely to produce favourable haemodynamic and hormonal effects in hypertensive patients.
 ...
PMID:Abrupt change from a beta-adrenoceptor blocking drug to enalapril in hypertension. 257 64

To determine the nature of the resultant effect on blood pressure when angiotensin converting enzyme (ACE) inhibitors are combined with other hypotensive agents in the treatment of uncomplicated essential hypertension, two randomized, double-blind, crossover trials were conducted. In each trial there were four treatment phases, each 4 weeks in duration, comprising a 2 X 2 factorial experiment. Twenty-one patients completed the first study in which the effects of enalapril (10 mg twice daily) were compared with hydrochlorothiazide (25 mg twice daily), with the two drugs in combination and with placebo. All blood pressure parameters were reduced in the three active treatment phases compared with placebo (P less than 0.001). Enalapril and hydrochlorothiazide were equally effective and in combination their hypotensive effects were fully additive. Sixteen patients completed the second study which compared the effects of enalapril (20 mg daily), atenolol (50 mg daily), the two drugs in combination and placebo. All blood pressure parameters were again reduced in all phases compared with placebo (P less than 0.001). Enalapril and atenolol were also equally effective, but in combination their hypotensive effects were less than fully additive, with attenuation of the potential additive response by 30-50%. These results indicate that a diuretic-ACE inhibitor combination can be expected to have a greater hypotensive effect than a beta-blocker-ACE inhibitor combination. Both hydrochlorothiazide and atenolol increased plasma atrial natriuretic peptide (ANP) concentrations (P less than 0.01), suggesting that ANP could contribute to the hypotensive effects of these two drug classes.
 ...
PMID:Treatment of hypertension with enalapril and hydrochlorothiazide or enalapril and atenolol: contrasts in hypotensive interactions. 283 75

Injection of atrial natriuretic peptide (ANP) induces marked diuresis, natriuresis and less marked blood pressure reduction. These effects are similar to those of renal kallikrein-kinin system (rKKS). In this study we investigated the influence of ANP on rKKS of rats. ANP was injected intravenously in male normotensive (WKy) and spontaneously hypertensive rats (SHRsp) as a bolus of 3.5 micrograms atriopeptin III. ANP induced, in both groups of rats, a marked increase in diuresis and natriuresis, while blood pressure decreased significantly. Renal plasma flow and urinary excretion of potassium increased only a little. The observed changes were similar in both strains of rats and there was no statistically significant difference except the lower potassium stimulation in the SHRsp than in the WKy (p less than 0.05). In regard to the basal activity of the rKKS there was a significant difference between the two strains of rats. The activity of renal kallikrein in urine and of kininase II in plasma was reduced in the SHRsp about 50%, while renal kinin excretion in urine was markedly enhanced in these rats, if compared to the WKy controls. In both groups of rats renal kallikrein and kinin excretion was stimulated by ANP for a short time and, simultaneously, total kininogen in plasma decreased after the injection of ANP. The increment of renal kallikrein excretion in urine was much less marked in the SHRsp than in the WKy rats. The reduced kallikrein stimulation was compensated by the reduced kinin degradation by kininase II in these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effect of atrial natriuretic peptide (ANP) on the renal kallikrein-kinin system in normotensive and spontaneously hypertensive rats]. 284 16

Removal of iodinated 28-amino acid atrial natriuretic peptide ([125I]ANP) by rabbit lungs was measured by indicator-dilution methods. After bolus injection of 6.5 pmoles of [125I]ANP, 66.9 +/- 2.9% was removed in a single pass through the lungs. Removal was unaltered by a kininase II inhibitor but was reversibly decreased by unlabelled ANP. Thus the lungs can remove ANP from the pulmonary circulation by a mechanism that does not involve hydrolysis by kininase II. Lungs therefore may be involved in regulating systemic concentrations and hence renal and other actions of ANP.
 ...
PMID:Removal of atrial natriuretic peptide by perfused rabbit lungs in situ. 294 98

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with organic heart disease undergoing diagnostic cardiac catheterization. Independent of nature and duration of the disease (valvular heart disease, congestive cardiomyopathy) plasma ANP levels were closely related to the severity of cardiac failure. Furthermore, plasma ANP levels were found to be negatively correlated with the cardiac index and to be positively correlated with right and/or left atrial and with pulmonary artery pressures. During physical exercise (bicycle ergometer) a marked increase of plasma ANP levels was observed, which was closely related to increments in mean pulmonary artery pressure. This rise in plasma ANP levels during physical exercise was not attenuated in patients with already elevated resting plasma concentrations of ANP. In patients with congestive cardiomyopathy, afterload-reduction by ACE-inhibition resulted in changes of central hemodynamics, which were closely reflected by venous concentrations of ANP. The measurement of plasma ANP levels may serve as an indicator of the severity of cardiac failure. Plasma concentrations of ANP, however, are neither helpful in establishing the etiology of the underlying heart disease nor in differentiating left and right heart failure. However, in cases of already established organic heart disease plasma ANP levels may be used as a marker for assessing the efficacy of the therapeutic regimen.
 ...
PMID:[Does the measurement of plasma ANP have a diagnostic or prognostic value in patients with organic heart disease?]. 297 Jan 74


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>