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)

6 healthy male subjects on a fixed salt-diet performed 1 hour ergocycle exercise at 65% of VO2 max in normoxic (N) and hypoxic (H) conditions. Blood samples were taken at intervals for estimations of plasma aldosterone (PAC), angiotensin converting enzyme (ACE), adrenocorticotrophic hormone (ACTH) and catecholamine concentrations. Plasma volume reductions with exercise were similar in N (4.3 +/- 1%) and H (4.0 +/- 1%). PRA response to exercise was increased by hypoxia while PAC and plasma catecholamine rose to a similar extent in both conditions. Increases in ACTH concentration occurred at the end of exercise but no difference was found between high and low altitudes. Plasma ACE remained unchanged throughout exercise in either condition. These results indicate that hypoxemia interferes with PRA-mediated aldosterone secretion. The variations in plasma ACTH levels during exercise in hypoxia do not appear responsible for this interference.
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PMID:Dissociated response of aldosterone from plasma renin activity during prolonged exercise under hypoxia. 284 20

The antihypertensive effect of a non-sulfhydryl, long acting ACE (angiotensin converting enzyme) inhibitor, MK-421, was evaluated by administering a single dose of 10 mg to 13 patients with mild to moderate essential hypertension. The pharmacokinetic profile of MK-421 and its potent active metabolite, MK-422, was also assessed, together with the effect on the various components of the renin-angiotensin system. A single dose of MK-421 produced a significant fall in MBP from 2 to 24 hours post-drug. As could be expected, plasma ACE activity was suppressed up to 24 hours after MK-421. The half-life of MK-422, Cmax and [AUC]24(0) of MK-421 and MK-422 were measured. No significant change in plasma bradykinin or urinary excretion rate of kallikrein was observed, whereas a slight increase was observed in the urinary excretion rate of kinins after MK-421 in 8 patients. Significant correlations were observed between pretreatment PRA levels and the maximum fall in MBP.
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PMID:Serum concentration and effects of a single dose of enalapril maleate in patients with essential hypertension. 298 51

To assess if dopaminergic control of aldosterone secretion is mediated by the renin-angiotensin system, the effect of chronic angiotensin converting enzyme inhibition by enalapril on the aldosterone response to metoclopramide has been studied in 10 patients with mild to moderate essential hypertension. Enalapril reduced supine blood pressure and increased the heart rate significantly. Plasma renin activity and urinary sodium excretion rose significantly. PRA was not changed by metoclopramide, neither during placebo nor during enalapril treatment. Metoclopramide induced a two-fold increase in plasma aldosterone, the peak response being reached within 15 min. Enalapril treatment did not alter the aldosterone response to metoclopramide. Dopaminergic control of aldosterone secretion appears to be independent of the renin-angiotensin system.
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PMID:Stimulation of aldosterone secretion by metoclopramide is not affected by chronic converting enzyme inhibition. 300 Jul 95

The present study was designed to clarify the role of serum angiotensin I-converting enzyme (ACE) in the occurrence and maintenance of hypertension in essential hypertension (EH). For this purpose, following experiments were carried out: 1) Correlations between serum ACE activity and renin activity (PRA), aldosterone concentration (PAC) and bradykinin concentration (PBC) in plasma, and blood pressure (BP) as well as serum creatinine levels. 2) Circadian rhythm of serum ACE activity. and 3) Effect of furosemide, upright posture, both furosemide and upright posture, propranolol, indomethacin, 9 alpha-fluorocortisol or angiotensin II (A-II) on the serum ACE activity, PRA, PAC and circulating plasma volume (CPV). The following results were obtained: The serum ACE activity was 30.2 +/- 5.0 U/ml (means +/- SD) in EH as a group, which was significantly higher than that (27.3 +/- 3.9 U/ml) in age matched normotensive subjects (NT) (p less than 0.001). While there was no significant difference in the enzyme activity between low-renin EH (LREH) and NT, a significant difference was found between normal- (NREH) or high-renin EH (NREH) and NT (p less than 0.05 for NREH, p less than 0.01 for HREH). A negative correlation was observed between enzyme activity and age in EH (r = -0.221, 0.05 less than p less than 0.10) as well as in NT (r = -0.306, p less than 0.05). No significant relationships were observed between enzyme activity and BP in either EH or NT. There was a significant positive correlation between enzyme activity and PRA in NT. (r = 0.501, p less than 0.001), NREH (r = 0.658, p less than 0.001) and HREH (r = 0.695, p less than 0.001). However, no significant relationship was found between them in LREH. The enzyme activity was significantly correlated to PAC in NT (r = 0.368, p less than 0.01), NREH (r = 0.567, p less than 0.001) and HREH (r = 0.529, p less than 0.01), but not in LREH. Although no significant correlation was observed between enzyme activity and PBC in NT, NREH and HREH, a significant relationship was found in LREH (r = -0.460, 0.05 less than p less than 0.10). The enzyme activity was not related to serum creatinine levels in EH as well as in NT. In NT, the serum levels of ACE activity reached a maximum values at 6:00 a.m. or 9:00 a.m., and gradually decreased between 6:00 p.m. and 3:00 a.m. An almost similar circadian rhythm of enzyme activity was found in EH.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Clinical significance of serum angiotensin I-converting enzyme in essential hypertension]. 300 63

The acute and long-term efficacy, tolerance and safety of two orally active angiotensin converting enzyme (ACE) inhibitors, captopril (C) and enalapril (E) were compared in patients on regular haemodialysis (RHD). C and E were successively administered for 6 months to 8 RHD patients with hypertension unresponsive to fluid withdrawal and conventional antihypertensive therapy. The fall in blood pressure after a starting dose of 25 mg C or 5 mg E was of the same magnitude. It was not correlated with the initial PRA levels, which were normal in all patients. The mean daily dose of ACE inhibitor was 45 +/- 28 mg during the C period and 19.4 +/- 17.6 mg at the end of the E period. Three patients required additional treatment, comprising beta-blockers and/or calcium antagonists. The individual daily dose of ACE inhibitor, the need for additional treatment and the antihypertensive response achieved were highly correlated during both study periods. During C administration 4 out of 8 patients presented a taste disturbance, which disappeared 2 weeks after substituting E for C. Serum electrolytes, liver enzymes, haemoglobin concentration and white cell and platelet counts remained unchanged throughout both study periods. It is concluded that RHD patients with hypertension are responsive to ACE inhibitors, C and E being equally effective.
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PMID:Intra-individual comparison of captopril and enalapril in patients undergoing regular haemodialysis. 301 37

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

The effects of three doses of perindopril (4.8 and 16 mg), a new angiotensin I-converting enzyme inhibitor, and of a placebo on systemic blood pressure, heart rate, brachial artery flow and diameter, forearm vascular resistance and the renin angiotensin system biological parameters (plasma converting enzyme activity PCEA, renin activity PRA and aldosterone PA) were compared during a double-blind cross-over study performed in six healthy volunteers. Perindopril dose-dependently inhibited PCEA, increased PRA, augmented brachial artery flow and diameter and decreased forearm vascular resistance, whereas it did not affect systemic blood pressure and heart rate. The perindopril-induced increase in brachial artery flow was related (a) at the low dose to the sole arteriolar and (b) at the two highest doses to both arteriolar and large vessels dilatation. Finally, during the ten first hours following drug intake, there was a significant correlation between perindopril-induced PCEA inhibition and brachial artery flow increase.
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PMID:[Peripheral hemodynamic and biological effects of perindopril in the healthy subject. Dose-effect relationship]. 302 73

The antihypertensive efficacy of ACE inhibitors depends in theory from the blockade of the angiotensin II formation but also from the inhibition of kinin breakdown. To test whether a blunted activity of the kallikrein-kinin system might account for the failure of ACE inhibitors in lowering BP in patients in whom the renin-angiotensin system is not enhanced, thirty-one essential hypertensives with normal or low PRA were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall both in systolic and diastolic blood pressure (BP) was obtained in the subgroup of patients who were classified as "normal kallikrein hypertensives" according to whether their pretreatment urinary kallikrein excretion was within the normal range, while no significant change in BP was observed in "low kallikrein hypertensives". Furthermore the mean percentage fall in mean BP, throughout the 2 hours following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47, p less than 0.05) in the entire group of patients. Our results suggest that a blunted activity of the kallikrein system might be responsible for failure of captopril in lowering BP in patients in whom the renin-angiotensin system is not pathogenetically implicated.
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PMID:Urinary kallikrein excretion can predict the blood pressure response to a single oral dose of captopril. 332 15

The mechanism of action of angiotensin converting enzyme (ACE) inhibitors to lower blood pressure remains unclear, but the weight of available data favour peripheral blockade of the formation of angiotensin II (AII). Previous work in rats has shown that the prodrug ACE inhibitor, enalapril (MK-421), lowered blood pressure most effectively when PRA was elevated [sodium deficiency, two-kidney, one figure 8 hypertension, diuretic-treated spontaneously hypertensive rats (SHR)]. In sodium-deficient rats, the enalapril-sensitive component of the blood pressure was greatly reduced after salt loading, and nephrectomy blocked the antihypertensive response to enalapril in SHR. In the present study, further support that the mechanism of action of enalapril involves a reduction in AII has been obtained from rats made hypertensive by continuous intravenous (i.v.) AII infusion for 10 days. Enalapril administered for seven days did not significantly lower blood pressure, suggesting that there were no important non-angiotensin mechanisms (such as bradykinin potentiation) involved in its action. From earlier studies in SHR, the time course for blockade of angiotensin I (AI) pressor responses and the blood pressure reduction did not correspond, suggesting a tissue site of action. In the present studies in adult SHR, a central site of action was ruled out since the parent inhibitor, enalaprilic acid (MK-422), injected into the brain ventricles did not acutely reduce blood pressure. An interaction of enalaprilic acid with the sympathetic nervous system was evaluated in dogs in which adrenergic activity was enhanced as a result of diuretic-induced renin release. Enlaprilic acid did not alter the enhanced hindquarter vasoconstrictor responses to sympathetic nerve stimulation. Enalapril increased renal blood flow, glomerular filtration rate and sodium excretion. The mechanism of the natriuresis in dogs probably involves several mechanisms including a decrease in aldosterone biosynthesis, changes in renal function (glomerular filtration rate and renal blood flow) and possibly blockade of a direct tubular effect of AII on sodium reabsorption. Enalaprlic acid was also studied in a closed chest dog model of acute left ventricular (LV) failure caused by embolization via the left main coronary artery with 50 microns plastic microspheres. Enalaprilic acid at 100 micrograms/kg i.v. reduced preload, afterload and improved LV performance without changing the heart rate. In conclusion, enalapril the prodrug, and enalaprilic acid the active inhibitor, are potentially useful in the treatment of hypertension and LV failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of action of enalapril in experimental hypertension and acute left ventricular failure. 610 Jun 9

Serum ACE-activity was studied in 27 young patients with uncomplicated essential hypertension. The possible importance of an increase in ACE for the pathogenesis of essential hypertension was evaluated by comparing the ACE levels to PRA, the plasma concentrations of angiotensin II and to the blood pressure lowering effect of captopril. Mean ACE-activity was slightly but significantly elevated in the hypertensive patients when compared to 28 normotensive control subjects. ACE-activity was not correlated to PRA, angiotensin II or the decrease in blood pressure following captopril. It is concluded that the increase in ACE-activity in essential hypertension is not of pathophysiological or clinical significance.
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PMID:Converting enzyme activity and essential hypertension. 630 33


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