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)

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

Serum angiotensin converting enzyme (ACE) activity and plasma renin activity (PRA) were studied during the development of the widespread necrotic arterial disease that occurs in the induction phase of one-kidney perinephritis hypertension. Control serum ACE activity was significantly higher in rabbits developing many arterial lesions than it was in rabbits developing relatively few arterial lesions. Serum ACE decreased 7 days after the production of unilateral perinephritis in all rabbits. Following contralateral nephrectomy, serum ACE decreased further in rabbits devloping many arterial lesions but returned toward control values in rabbits developing relatively few arterial lesions. Significant inverse correlations were demonstrated for the total number of arterial lesions that developed relative to a) the decrease in serum ACE activity 7 days after the production of unilateral perinephritis, b) the lowest or the average serum ACE activity during the period of development of the arterial lesions after contralateral nephrectomy, and c) the change in serum ACE activity during the period of development of the arterial lesions. Chronic treatment with SQ 20,881, a synthetic nonapeptide inhibitor of ACE activity, during the period of development of the hypertension and the arterial lesions significantly reduced the serum ACE activity and the hypertension but did not change interrelationships between serum ACE activity and the number of arterial lesions that developed. PRA significantly decreased after the production of perinephritis and decreased somewhat further during the induction period of the hypertension after contralateral nephrectomy. No relationships were demonstrated between PRA, or changes in PRA, and the development of arterial lesions. The increase in blood pressure during the incubation period of the hypertension did not correlate with the number of arterial lesions that developed. These finding indicate that serum ACE activity reflects importantly on the capacity to develop necrotic arterial lesions during the induction phase of one-kidney perinephritis hypertention and on functional events relating to their pathogenesis.
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PMID:Serum angiotensin converting enzyme activity and the capacity to develop hypertention-associated arterial disease. Studies during the induction phase of one-kidney perinephritis hypertension in rabbits. 21 77

Goat antibodies developed against pure rabbit pulmonary angiotensin-converting enzyme (peptidyl dipeptidase, EC 3.4.15.1) were administered intravenously to rats with two-kidney Goldblatt hypertension and to normotensive animals. In the hypertensive model these antibodies were associated with a sustained, immune-dependent decrease of blood pressure to normal values. A smaller, but also immune-specific, reduction of blood pressure was observed in the normotensive group. The data suggest that heterologous antibody directed against angiotensin-converting enzyme may provide a biologically specific probe for examining the contribution of the renin-angiotensin system to normal and pathologic circulatory states.
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PMID:Reversal of renovascular hypertension by antibodies specific for angiotensin-converting enzyme. 21 95

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

Serum angiotensin converting enzyme activity was assayed by a spectrofluorometric method in 19 patients with chronic renal failure on long term hemodialysis and 19 control subjects. Converting enzyme activity was increased in 11 of 19 (58%) patients compared with the controls (p less than 0.005). There was no correlation between serum converting enzyme activity and plasma renin activity or blood pressure in the patients. Possible mechanisms responsible for the increased converting enzyme activity are discussed.
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PMID:Serum angiotensin converting enzyme activity in patients with chronic renal failure on long term hemodialysis. 21 70

The effect of acute administration of SQ 14,225, a new angiotensin converting enzyme inhibitor, on the drinking response of female rats administered either isoprenaline, angiotensin I, or angiotensin II was studied during 2 h after treatment. Administration of isoprenaline (25 micrograms/kg body wt) was accompanied by a significant increase in water intake when compared with saline-treated controls. Acute administration of a constant dose of isoprenaline (25 micrograms/kg body wt) and increasing doses of SQ 14,225 (5--50 mg/kg) was accompanied by a dose-related, linear decrease in water intake. Acute administration of either angiotensin I or angiotensin II (200 micrograms/kg body wt) was accompanied by a significant increase in water intake. The dipsogenic response to angiotensin II was not affected by acute administration of 35 mg SQ 14,225/kg body wt. However, at the same dose of SQ 14,225, angiotensin I-induced thirst was attenuated. Since isoprenaline-induced and angiotensin I-induced, but not angiotensin II-induced, thirsts are blocked by SQ 14,225, the results suggest that isoprenaline-induced thirst is mediated by way of the renin--angiotensin system.
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PMID:Effect of an angiotensin converting enzyme inhibitor (SQ 14,225) on beta-adrenergic and angiotensin-induced thirsts. 22 56

1. Isoprenaline hydrochloride injected subcutaneously in rats given a choice test of 1.8% NaCl and water, first induced saline intake which started immediately and was almost concluded in 15 min, followed by a copious water intake. When either saline or water were given in a separate test, saline intake surpassed the water intake in the first 15 min.2. The delay of 15, 30 or 60 min after injection of isoprenaline, 100 mug/kg, before drinking was allowed, significantly reduced saline intake but did not modify the amount of water subsequently drunk.3. Isoprenaline caused a sudden drop in arterial blood pressure, the extent and duration depending on the dose. The time of maximum drop 3-4 min after injection coincided with the time the rat drank salt.4. Isoprenaline-induced saline drinking was significantly reduced after bilateral nephrectomy but water intake was unaffected.5. The beta-adrenoceptor blocking agent, propranolol, inhibited isoprenaline-induced NaCl and water intake, while the alpha-adrenoceptor antagonist phenoxybenzamine abolished isoprenaline-induced NaCl intake and enhanced water intake.6. Saralasin acetate (P-113), a competitive inhibitor of angiotensin II, given into the third brain ventricle, prevented the isoprenaline-induced NaCl and water intake as well as angiotensin II-induced drinking. The angiotensin converting enzyme inhibitor SQ-20881 reduced the isoprenaline-induced NaCl and water intake.7. In conclusion, hypotension might be a component of salt drinking evoked by isoprenaline although the dipsogenic action of beta-stimulation is mainly due to endogenous renin-angiotensin activation.
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PMID:Drinking behaviour in rats treated with isoprenaline, angiotensin II or angiotensin antagonists. 23 Nov

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

1. Captopril was shown to be as effective as hydrochlorothiazide in lowering the blood pressure in patients with moderately severe essential hypertension. 2. With the combination of captopril and hydrochlorothiazide satisfactory control of blood pressure was maintained over 8 months. 3. Inhibition of angiotensin converting enzyme by captopril in man was associated with falls in plasma angiotensin II and urinary aldosterone and rises in angiotensin I and plasma renin. 4. No change in venous concentrations of bradykinin could be demonstrated during therapy. 5. Captopril attenuated the hyperaldosteronism and hypokalaemia associated with diuretic therapy.
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PMID:Hormonal changes with long-term converting-enzyme inhibition by captopril in essential hypertension. 23 17

The short-term cardiovascular and endocrine effects of an orally active angiotensin converting enzyme inhibitor, SQ14,225, were evaluated in 17 subjects with drug-resistant hypertension (10 with essential and seven with renovascular hypertension). On normal dietary sodium, SQ14,225 (after 3 days at average dose of 664 mg/day) reduced mean arterial pressure (MAP) significantly (from 141 +/- 4 to 122 +/- 4 mm Hg, (SE), p less than 0.001). However, only eight of the patients achieved blood pressures within the normotensive range. Of eight patients with residual hypertension, seven exhibited further decreases in MAP (from 132 +/- 4 to 108 +/- 6 mm Hg (SE), p less than 0.001) when dietary sodium was reduced to 10 mEq/day. No rebound hypertension was noted when treatment was temporarily discontinued for 3 days in 11 patients. The reductions in blood pressure were not associated with either orthostatic hypotension or interference with baroreceptor reflexes. The values of supine plasma renin activity (PRA) were not always predictive of blood pressure responsiveness to the drug. With treatment, plasma aldosterone concentrations (PAC) decreased modestly (values from 40 +/- 9 to 22 +/- 3 ng/dl (SE), p less than 0.05). The plasma concentrations of cortisol, norepinephrine and serum potassium were left unchanged during the period of studies. The present study has not defined the exact mechanism by which SQ14,225 lowered blood pressure. Nevertheless, it indicates that this agent may be a practical therapeutic adjunct in the treatment of certain subsets of the human hypertensive population. The lack of serious interference with cardioscular and humoral homeostasis adds to its attractiveness as a therapeutic agent.
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PMID:Converting enzyme inhibition with an orally active compound in hypertensive man. 23 90


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