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)

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

It has been suggested that AII-mediated renal mechanisms limit the efficacy of moderate sodium restriction in the lowering of blood pressure (BP) in hypertension. We therefore studied renal hemodynamics and sodium handling in nine essential hypertensives in balance on 200 and on a 50 mmol sodium diet, before and during ACE-inhibition (enalapril 10 mg bid for 8 days) in a cross-over fashion. BP was similar on 50 and 200 mmol Na before enalapril, the fall in BP during enalapril was significantly more pronounced on 50 mmol Na. On 50 mmol Na, GFR and filtered Na were significantly lower, and tubular reabsorption was significantly higher than on 200 mmol Na. GFR increased during enalapril in 50 but not on 200 mmol Na. Consequently, the differences in GFR and filtered load elicited by sodium restriction were no longer present during ACE-inhibition. In contrast, the differences in tubular reabsorption between 50 and 200 mmol Na persisted during enalapril. In conclusion, moderate sodium restriction, not affecting BP, can elicit a renal hemodynamic response. As this response is blunted by ACE-inhibition it is probably mediated by AII. This blunting may contribute to the increased sodium sensitivity of BP during ACE-inhibition. The adaptation of tubular sodium reabsorption is not affected by ACE-inhibition.
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PMID:Moderate sodium restriction in hypertensive subjects: renal effects of ACE-inhibition. 303 89

In Inactin-anaesthetized rats inhibition of angiotensin converting enzyme by captopril resulted in a small decrease in mean arterial blood pressure accompanied by increases in the rates of glomerular filtration, water and electrolyte excretion. Infusion (100 pmol/min) of sar1-leu8-angiotensin II (sar1-leu8-AII) during continuing converting enzyme blockade reversed these changes in renal function but had no effect on arterial blood pressure. The data indicate that sar1-leu8-AII has partial agonist activity in the kidney although it acts as an antagonist of AII in the systemic circulation. This supports the proposal that angiotensin receptors within the kidney differ from those in the peripheral circulation.
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PMID:Sar1-leu8-angiotensin II reverses the effects of captopril on renal function in rats. 351 18

The role of central angiotensin converting enzyme (ACE), in the maintenance of high blood pressure, was examined in unanesthetized spontaneously hypertensive rats (SHR). Pressor and dipsogenic responses induced by intracerebroventricular (ICV) injections of angiotensin I (AI) were elicited before and 30 min after either captopril (120-800 nanomoles ICV), enalapril (66-460 nanomoles ICV) and enalaprilic acid (70-280 nanomoles ICV). Enalapril was 1.6 (0.7-3.9) and 1.7 (0.9-2.9) times more potent than captopril in inhibiting AI-induced pressor and dipsogenic responses, respectively. Enalaprilic acid was 2.7 (1.1-7.1) and 2.9 (1.9-4.8) times more potent than captopril in inhibiting AI- (ICV administration) induced pressor and dipsogenic responses, respectively. None of the ACE inhibitors, in contrast, reduced the central actions of AII. Basal mean arterial pressure was not reduced by these ACE inhibitors after ICV administration. Administered orally at doses which produced similar hypotensive responses, neither captopril (30 mg/kg) nor enalapril (3 mg/kg) blocked the responses induced by AI given ICV (10 ng). These findings indicate that ACE inhibitors given acutely do not penetrate into the central nervous system sufficiently to block the dipsogenic and pressor responses induced by AI given ICV, and suggest that inhibition of central ACE may not be important to the acute antihypertensive activity of the ACE inhibitors tested.
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PMID:Comparative effects of enalapril, enalaprilic acid and captopril in blocking angiotensin I-induced pressor and dipsogenic responses in spontaneously hypertensive rats. 608 83

We assessed the antihypertensive and hormonal effects of two new angiotensin converting enzyme (ACE) inhibitors, enalapril (MK-421) and lisinopril (MK-521) in 22 patients with renovascular hypertension. All patients had angiographically verified renal artery lesions, 3 had bilateral renal artery stenosis and one a stenosis in a single kidney, and the rest had unilateral renal artery stenosis. After placebo treatment for 3 days in hospital, increasing doses from 5 to 40 mg daily, of both ACE-inhibitors were given. Both drugs induced a significant fall in blood pressure (BP). Significant BP reductions were seen after 2 h with a maximum fall for the enalapril group at a dose of 40 mg 4 h after drug intake (mean supine BP decrease - 31/24 mm Hg, standing - 29/16 mmHg). The corresponding maximal BP reductions were for the lisinopril group at a dose of 40 mg o.d. at 6 h: mean supine BP fall - 25/28 mmHg and standing - 33/31 mm Hg. Both drugs significantly inhibited serum ACE to about 5 to 10% of initial values and with a duration for more than 24 h. Both drugs also caused a decrease in plasma-AII levels and also in plasma aldosterone concentrations. There were not toxic effects and no serious side effects. Careful monitoring of biochemical variables showed no significant changes. We conclude that both enalapril and lisinopril are effective and very safe agents for the treatment of renovascular hypertension and with a long duration of action and with very good tolerance.
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PMID:Enalapril and lisinopril in renovascular hypertension--antihypertensive and hormonal effects of two new angiotensin-converting-enzyme (ACE) inhibitors. A preliminary report. 608 7

The synthetic tetradecapeptide renin substrate (TDP; Asp-arg-val-tyr-ile-his-pro-phe-his-leu-leu-val-tyr-ser) has been employed frequently to elucidate the enzymatic action of renin in vitro and, to a lesser extent, in vivo. We assessed the utility of TDP as a renin substrate in vivo using conscious spontaneously hypertensive rats. Intravenous injection of TDP (1 and 3 micrograms/kg) increased diastolic pressure by 45 +r2 and 67 +/- 2 mmHg, respectively. The pressor response to TDP was significantly inhibited by captopril (3 mg/kg, po), indicating its dependence on conversion by ACE to some active molecule. Pressor responses to TDP also were less in animals subjected to bilateral nephrectomy 18-24 hr before study. However, responses to angiotensin I and II also were reduced, implying a non-specific effect of nephrectomy. Intravenous infusion of the renin inhibitor pepstatin (200 micrograms/min) inhibited pressor responses to hog renin by approximately 60%, but did not affect those to TDP. Intravenous infusion of the water soluble renin inhibitor, pepstatinyl-arginine-o-methyl ester (500 micrograms/min), also inhibited pressor responses to renin (approx. 80%) and did not affect those of TDP. Incubation to TDP (5 microM) with rabbit lung ACE resulted in generation of AI that was blocked by captopril (1 microM). These data suggest that TDP is a substrate for ACE and that the increase in blood pressure produced by TDP is due to its sequential cleavage by ACE to AII and can be independent of renin.
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PMID:Mechanism of the pressor response to tetradecapeptide renin substrate in the rat. 609 83

There are several approaches for interfering with the renin-angiotensin system. Antibodies against renin and angiotensins I and II (AI and AII) have not been consistently successful in the past, probably because of nonspecific effects; however, recent purification of renin now makes this approach more promising. Renin inhibitors include pepstatin and analogs, lipids and phospholipids, and renin-substrate analogs. Pepstatin and analogs are the most potent and specific but they are not orally active. The phospholipids are the most effective in vivo but their specificity is yet to be established. Renin-substrate analogs have been developed that have biologically significant effects but are not orally active. Some of the most potent and specific agents available for interfering with the renin-angiotensin system are the AII receptor antagonists. While these compounds effectively prevent the actions of AII, they suffer from several severe deficiencies: partial agonist activity, short duration of action, and lack of oral activity. The recent development of angiotensin-converting enzyme (ACE) inhibitors that are orally active has provided the greatest degree of clinical success for inhibitors of the renin-angiotensin system and, consequently, the impetus to develop still better compounds. Captopril (SQ 14,225) is the prototype ACE inhibitor, being highly potent and specific with no other demonstrated pharmacological activity. Captopril is effective in all forms of human and animal models of hypertension except mineralocorticoid hypertension, which requires concomitant diuretic therapy. Because ACE is the same enzyme as kininase II, the enzyme that degrades kinins, the possibility exists that kinins are involved in the cardiovascular action of captopril, although this prospect is unlikely.
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PMID:Inhibitors of the renin-angiotensin system as new antihypertensive agents. 617 73

There are several approaches for interfering with the renin-angiotensin system. Antibodies against renin angiotensins I and II (AI and AII) have not been consistently successful in the past, probably because of nonspecific effects; however, recent purification of renin now makes this approach more promising. Renin inhibitors include pepstatin and analogs, lipids and phospholipids, and renin-substrate analogs. Pepstatin and analogs are the most potent and specific but they are not orally active. The phospholipids are the most effective in vivo but their specificity is yet to be established. No renin-substrate analogs have been developed that have biologically significant effects. Some of the most potent and specific agents available for interfering with the renin-angiotensin system are the AII-receptor antagonists. While these compounds effectively prevent the actions of AII, they suffer from several severe deficiencies: partial agonist activity, short duration of action, and lack of oral activity. The recent development of angiotensin-converting enzyme ACE) inhibitors that are orally active has provided the greatest degree of clinical success for inhibitors of the renin-angiotensin system and, consequently, the impetus to develop still better compounds. Captopril (SQ 14,225) is the prototype ACE inhibitor, being highly potent and specific with no other demonstrated pharmacological activity. Captopril is effective in all forms of human and animal models of hypertension except mineralocorticoid hypertension, which requires concomitant diuretic therapy. Because ACE is the same enzyme as kininase II, the enzyme that degrades kinins, the possibility exists that kinins are involved in the cardiovascular action of captopril, although this prospect is unlikely.
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PMID:Drugs inhibiting the renin - angiotensin system. 626 16

The components of the renin-angiotensin system exist in the brain but their physiological role is uncertain. The effects of two angiotensin converting enzyme (ACE) inhibitors, MK 421 (or its diacid) and captopril, on brain ACE activity, as measured by inhibition of the pressor response to intracerebroventricularly (i.c.v.) administered angiotensin I (AI), and the potential contribution of the central nervous system to their antihypertensive activity were evaluated in the present series of experiments. The diacid of MK 421 (1 and 10 micrograms) and captopril (3 and 10 micrograms) given i.c.v. to conscious normotensive rats reduced the pressor response to i.c.v. AI indicating that they can inhibit brain ACE. Responses to AII were unaffected. Oral administration of maximal antihypertensive doses of MK 421 (10 mg/kg) and of captopril (30 mg/kg) to normotensive rats did not attenuate pressor responses to i.c.v. AI indicating that brain ACE was not inhibited under these circumstances. Intracerebroventricular administration of MK 421 diacid, (10 and 30 micrograms) and captopril (30 and 100 micrograms) did not lower baseline blood pressure of spontaneously hypertensive rats. These experiments indicate that MK 421 and captopril can inhibit brain ACE but that the central renin-angiotensin system probably does not contribute to their antihypertensive activity.
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PMID:Attenuation of pressor responses to intracerebroventricular angiotensin I by angiotensin converting enzyme inhibitors and their effects on systemic blood pressure in conscious rats. 630 May 78

The chronic effects of oral administration of an angiotensin converting enzyme inhibitor (captopril, 63-80 mg/Kg/day) on blood pressure and the renin-angiotensin-aldosterone system were-studied in normotensive male Wistar rats. Blood pressure (BP), plasma renin activity (PRA), plasma renin concentration (PRC), plasma renin substrate concentration (PRS), plasma aldosterone concentration (PAC) and renal renin content (RRC) were measured after 2, 9, 19, 29 and 58 days of captopril administration. BP was determined in awake rats and blood samples were obtained by decapitation. In addition, BP responses to bolus injections of angiotensin I (AI, 80 ng/Kg), angiotensin II (AII, 80 ng/Kg) and bradykinin (BK, 10 micrograms/Kg) were examined in conscious rats which had received captopril for 20 days. The BP of the rats which had been given captopril for 9 days or longer was significantly lower than that of the control rats. PRA and PRC were markedly increased, and both PRS and PAC were decreased in the captopril-treated rats. RRC, which was reduced after 2 days of captopril administration, was substantially increased thereafter. Although the pressor responses to AII were similar in the captopril treated and the control rats, the responses to AI were reduced to 50% of those to AII in the former. The depressor responses to BK in the captopril-treated rats were 2.3 times as large as those in the control rats. Our results show that long-term use of captopril lowers BP in normotensive rats on a normal sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of chronic administration of captopril on blood pressure and the renin-angiotensin-aldosterone system in normotensive rats. 635 79


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