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)

Indirect systolic blood pressure (SBP) was monitored in 9 groups of 15 male conscious 2-kidney renal hypertensive rats (RHR) for over 6 months. Daily oral dosing with captopril (SQ 14,225, D-3-mercapto-2-methylpropanoyl-L-proline, 30 mg/kg), an orally active angiotensin I-converting enzyme inhibitor, lowered SBP 30--50 MM Hg during this period. Withdrawal of captopril for 5 days at 1, 3 and 6 months resulted in gradual return of SBP to control levels without overshoot. Resumption of dosage with captopril again decreased SBP. Daily oral dosing with hydrochlorothiazide (HCTZ, 6 mg/kg/day) alone for 6 months had little or no effect on SBP, but increased the antihypertensive effect of captopril. Daily oral dosing with hydralazine (6 mg/kg) caused an initial marked antihypertensive effect greater than that of captopril but almost complete tolerance developed within 4 weeks of dosing. Highest survival rates occurred in RHR treated with captopril plus HCTZ. In four other similarly treated groups of RHR and normotensive rats (NR), least cardiac hypertrophy and highest plasma renin activity occurred in captopril-treated animals compared with vehicle-treated controls. Plasma renin activity was about 2 to 4 fold higher in the rats dosed with captopril compared with vehicle-treated rats. Heart weight/body weight ratios, initially higher in the two RHR groups compared to NR, decreased only in the captopril treated group to or near those of the NR groups. These results indicate that chronic treatment with captopril decreased SBP and cardiac weights of RHR, and that HCTZ, or possibly other diuretics, can augment the antihypertensive effect of captopril while having little or no effect by themselves.
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PMID:Chronic antihypertensive effects of captopril (SQ 14,225), an orally active angiotensin I-converting enzyme inhibitor, in conscious 2-kidney renal hypertensive rats. 21 96

Peptide inhibitors of angiotensin I-converting enzyme (peptidyldipeptide hydrolase, EC 3.4.15.1) were produced by digesting gelatin with bacterial collagenase. The inhibitors were isolated from the digests with a combination of alcohol fractionation, treatment with Amberlite CG-50 column, gel filtration through Sephadex G-25, and Dowex 50 column and paper chromatography. Nine peptide fractions were purified to apparent homogeneity judging by thin-layer and ion-exchange column chromatography, and amino acid composition. Amino acid sequences of the peptides were determined: 2 were found to be mixtures of peptides and the sequence of another was only partially determined. Six of the peptides were potent inhibitors of the converting enzyme, while the other three were less active. 6 peptides were substrates for the enzyme. The enzyme released a dipeptide, Ala-Hyp from one peptide and was strongly inhibited by this dipeptide. The remainder of the parent peptides was a less effective inhibitor.
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PMID:Peptide inhibitors of angiotensin I-converting enzyme in digests of gelatin by bacterial collagenase. 21 31

Brattleboro rats homozygous for hypothalamic hereditary diabetes insipidus (DI rats) were used to investigate the following questions: a) Do exogenous and endogenous angiotensin II (AII) have an antidiuretic effect in diabetes insipidus? b) Does AII mediate the antidiuresis induced by furosemide? The following results were obtained: 1. AII (5 mg/kg s.c. in oil) and furosemide (50 mg/kg i.p.) decreased urine flow and increased urinary sodium excretion. Furosemide led to a two-fold increase of AII plasma concentrations and a decrease of plasma sodium levels. 2. SQ 14 225 (2 x 2.5 mg/kg p.o.), an angiotensin I-converting enzyme inhibitor, led to an increase of urine flow and to a slightly elevated urinary sodium excretion. 3. When the formation of AII was blocked by SQ 14 225 (2 x 2.5 mg/kg p.o.), AII plasma concentrations were 2.5-fold decreased, but furosemide still reduced urine flow. We conclude that plasma AII might have an antidiuretic action in DI rats. However, AII does not mediate the antidiuresis induced by furosemide.
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PMID:Inhibition of the renin-angiotensin-system in Brattleboro rats with hereditary hypothalamic diabetes insipidus. 21 21

Kininase II (angiotensin I-converting enzyme) is generally accepted to be the enzyme responsible for the conversion of angiotensin I (A I) to angiotensin II (A II). This study examined the response of the microvasculature of the hamster cheek pouch to the local application of A I, A II, and the renin substrate, tetradecapeptide (TDP). A I and TDP caused a localized vasoconstriction that was not blocked by converting enzyme inhibitors (CEI: BPF5a for A I and BPF5a and the nonapeptide inhibitor for TDP). However, both the A II antagonist [Sar1, Ala8]angiotensin II and the antiserum to A II blocked completely the A I- and TDP-induced vasoconstriction. Sixty-eight percent of the applied A I was converted to A II in the presence of CEI as well as in its absence. It is concluded that the vasculature of the hamster cheek pouch converts significant amounts of A I to A II by a route that does not involve kininase II.
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PMID:Direct evidence for the presence of a different converting enzyme in the hamster cheek pouch. 21 48

The method of chemical assay of angiotensin I-converting enzyme described is a modification of the previously published spectrophotometric assay based on quantitation of hippuric acid released from hippuryl-L-histidyl-L-leucine. The new procedure involves extraction of hippuric acid with ethylacetate, evaporation to dryness of the extract, solubilization of the residue with 1 mol/l NaCl and purification with petroleum ether before measurements of the absorbance at 228 nm of the aqueous phase. Under these conditions, hippuric acid insoluble in petroleum ether remains in the aqueous phase, whereas other A228-absorbing materials, readily soluble in the ether and able to interfere with the assay, are eliminated.
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PMID:[Spectrophotometric assay of angiotensin I-converting enzyme (author's transl)]. 22 23

Purification of angiotensin I-converting enzyme from human lung and characteristics of the enzyme was studied. Experimental pneumonitis was produced in rabbits and the change of the activity of angiotensin I-converting enzyme was studied in purpose to clarify the role of this enzyme in the metabolism of vasoactive peptides in the lung. Purification was performed using trypsin treatment, acid treatment, DE52-cellulose column chromatography, hydroxyapatite chromatography and Sephadex G-200 gel filtration. The enzyme after final step showed a single band on disc gel electrophoresis. Experimental pneumonitis was produced by injection of Complete Freund's adjuvant (acute pneumonitis) and of N-nitroso-N-methylurethane (chronic pneumonitis). In acute experiment, angiotensin I-converting enzyme activity in pulmonary tissue and in plasma was significantly decreased. In perfusion experiment, conversion of angiotensin I to angiotensin II and inactivation of bradykinin were also significantly decreased. In case of decreased activity of angiotensin I-converting enzyme in the lung, less angiotensin II will be released into systemic circulation and bradykinin will pass through the pulmonary circulation into systemic circulation, thus this may result in the decrease of systemic blood pressure.
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PMID:Purification and properties of angiotensin I-converting enzyme in human lung and its role on the metabolism of vasoactive peptides in pulmonary circulation. 22 10

The effects of hydralazine (3 mg/kg) and the angiotensin I-converting enzyme (ACE) inhibitor captopril (SQ 14,225) (100 mg/kg) on mean arterial blood pressure, plasma renin activity, urinary volume and urinary Na+,K+, and aldosterone concentrations were examined in spontaneously hypertensive rats of the Okamoto and Aoki strain (SHR) after oral daily dosing for 2 weeks, 3 or 6 months. Captopril caused progressive cumulative reductions in blood pressure resulting in normalization of pressure after 6 months of dosing. Hydralazine also significantly reduced blood pressure but not to the level of normotensive rats of the Wistar-Kyoto strain (WKY). Reductions in heart size paralleled the changes in blood pressure, normalization of cardiac hypertrophy occurring after captopril but not hydralazine. Plasma renin activity increased approximately 2-3 fold after hydralazine and 15-fold after captopril. Neither hydralazine nor captopril had any consistent effects on 24-hr urine volume, urinary Na+,K+ or aldosterone excretion. These results indicate that chronic inhibition of ACE with captopril induces normalization of blood pressure in SHR, a normal-renin model of hypertension.
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PMID:Effects of chronic treatment with captopril (SQ 14,225), an orally active inhibitor of angiotensin I-converting enzyme, in spontaneously hypertensive rats. 23

Effects of an orally active angiotensin I-converting enzyme inhibitor, SQ 14225, on the actions of angiotensin I (AI) infused intravenously for 120 to 390 min were studied in 5 normal men. When 20 ng/kg/min of AI infusion was started immediately after a single oral administration of 100 mg of SQ 14225, a significant rise in blood pressure (BP) was observed for the first 15 min, but BP began to fall from 17 min and returned to the pretreatment level at 45 min. This BP level continued at least to 120 min and in one subject to 180 min. In this subject BP began to rise again from 185 min and reached the level of 15 min at 390 min. Plasma AI level increased gradually from 45 min. At 15 min plasma renin activity (PRA) decreased and plasma aldosterone (PA) increased, but then PRA began to increase and PA began to decrease. At 120 min the values of PRA and PA were similar to the pretreatment values. In one subject plasma AI and PRA began to decrease and PA began to increase after 120 or 180 min. On the other hand, in the 5 men sole AI infusion caused a continued BP rise, PRA decrease and PA increase, and sole SQ 14225 administration caused increases in plasma AI and PRA and a decrease in PA but no BP change. From these results it was concluded that complete blockade and partial inhibition of AI conversion by 100 mg of oral SQ 14225 lasted for about 2.5 and 6.5 hr, respectively and that BP rise, PRA suppression and aldosterone stimulation after AI infusion were entirely due to the actions of angiotensin II converted from AI.
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PMID:Effects of angiotensin I-converting enzyme inhibitor, SQ 14225, in nomal men. 38 75

1. The renal artery of conscious dogs was acutely narrowed over 30 s to reduce renal artery pressure distal to the stenosis to 40 mmHg and the stenosis was maintained for 1 h. The distal renal artery pressure was rapidly restored to a plateau slightly below pre-stenosis values within 10--15 min. Rises in systemic blood pressure and plasma renin activity were small and transient. 2. This restoration was an active process, mediated by the intrarenal effects of angiotensin II (AII), since it was greatly diminished or abolished when the renal artery was narrowed in the presence of angiotensin I-converting enzyme inhibitor or angiotensin receptor antagonist (1-Sar-8-Ile AII). However, it was not diminished by 'total' autonomic effector blockade. 3. This angiotensin II-mediated restoration of renal artery pressure may be of homeostatic significance for the maintenance of glomerular filtration rate.
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PMID:Intrarenal action of angiotensin II in restoring renal artery pressure after acute renal artery stenosis. 72 9

The aldosterone and arterial pressure response to long-term infusion of two angiotensin II inhibitory analogues, [Sar1,Ala8]angiotensin II and [Sar1,Ile8]angiotensin II, and the angiotensin I-converting enzyme inhibitor, SQ 20,881, was studied in conscious dogs during sodium deficiency. Plasma aldosterone concentration (PAC), plasma cortisol concentration (PCC), and plasma renin activity (PRA) were determined by radioimmunoassay. In conscious dogs after dietary sodium restriction (5 mEq of Na+/day) for 21 days, PAC averaged 37.5 +/- 8.9 (mean +/- SE) ng/dl, PCC averaged 1.3 +/- 0.5 microng/dl, PRA averaged 3.23 +/- 0.42 ng/ml per hour, and arterial blood pressure (AP) averaged 103 +/- 5 mm Hg. During long-term infusion of [Sar1,Ala8]angiotensin II (5 microng/kg min-1), PAC averaged 34.7 +/- 8.5 ng/dl, PCC averaged 1.5 +/- 0.5 microng/dl, PRA averaged 16.4 +/- 3.1 ng/ml per hour, and AP averaged 88 +/- 5 mm Hg. During long-term infusion of [Sar1,Ile8]angiotensin II (5 microng/kg min-1), PAC averaged 45.8 +/- 12.6 ng/dl, PCC averaged 1.75 +/- 0.5 microng/dl, PRA averaged 13.6 +/- 4.3 ng/ml per hour, and AP averaged 86 +/- 5 mm Hg. During long-term infusion of angiotensin I-converting enzyme inhibitor (5 microng/kg min-1), PAC averaged 14.9 +/- 4.8 ng/dl, PCC averaged 1.75 +/- 0.5 microng/dl, PRA averaged 20.3 +/- 5.3 ng/ml per hour, and AP averaged 76 +/- 5 mm Hg. The intrinsic agonistic properties of the angiotensin II inhibitory analogues on the adrenal cortex negate their use for defining the role of the renin-angiotensin system in the regulation of aldosterone biosynthesis during sodium deficiency. The precipitous fall in aldosterone secretion and arterial blood pressure during long-term infusion of angiotensin I-converting enzyme inhibitor demonstrates the importance of the renin-angiotensin system in mediating aldosterone biosynthesis during sodium deficiency and the essential role of the renin-angiotensin-aldosterone system in the regulation of arterial pressure during sodium deficiency.
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PMID:Role of the renin-angiotensin system in the regulation of aldosterone biosynthesis and arterial pressure during sodium deficiency. 87 Feb 26


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