Inhibition of angiotensin converting enzyme by SQ 14,225 in conscious rabbits

Murthy, Vishnu; Waldron, Thomas L.; Goldberg, M. E.; Vollmer, Regis R.

doi:10.1016/0014-2999(77)90335-1

Cited by 101 publications

(59 citation statements)

References 17 publications

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“…Therefore captopril, an orally active converting-enzyme inhibitor, has the potential not only for antagonizing the generation of the vasoconstrictor angiotensin II, but also for impairing the catabolism of bradykinin, a potent vasodilator. Bradykinin releases vasodilating and natriuretic prostaglandins from renal and other tissues, an effect that is enhanced by captopril (Murthy et al, 1978). Therefore, prostaglandins may theoretically play a part in the haemodynamic actions of captopril.…”

Section: Introduction Methodsmentioning

confidence: 99%

Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition.

Silberbauer¹,

Stanek²,

Templ³

1982

Brit J Clinical Pharma

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1 A study was carried out to investigate the possible contribution of prostaglandins in captoprilinduced hypotension. 2 Healthy volunteers and patients with essential hypertension were given single oral doses of 25 mg and 50 mg captopril respectively before and after cyclo-oxygenase inhibition with indomethacin. 3 The acute hypotensive effect of captopril was not associated with changes in heart rate. As expected, captopril led to an increase in plasma renin activity, decrease in plasma angiotensin II, and decrease in plasma aldosterone concentration. 4 After acute indomethacin pretreatment the acute hypotensive effect of captopril was significantly blunted in volunteers and in the 14 hypertensive patients. Changes in plasma renin activity and angiotensin II were significantly lower from a lower baseline. 5Prostaglandins may therefore be mediators of the initial captopril effect. The blunting effect of indomethacin should be taken into account under clinical conditions.

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Section: Introduction Methodsmentioning

confidence: 99%

Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition.

Silberbauer¹,

Stanek²,

Templ³

1982

Brit J Clinical Pharma

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“…Erythrocytes labelled with "Cr according to the method of Strumia et al 8 were injected in a volume of 0.1 ml into the left ventricle. A blood sample of precisely 1.0 ml was drawn 10 minutes later, and radioactivity (RA) was measured in a gammaspectrometer (Packard, Modumatic II Auto Gamma, model 5320).…”

Section: Measurement Of Circulating Blood Volumementioning

confidence: 99%

“…1 a The acute antihypertensive action of the agent is attributed to a decrease of total peripheral resistance, 8 but the extent to which each vascular bed contributes to the decrease of total peripheral resistance is not known. There are no data available on hemodynamic effects of chronic blockade of ACE, despite the fact that antihypertensive drugs are clinically used on a long-term basis.…”

mentioning

confidence: 99%

Effects of long-term blockade of angiotensin converting enzyme with captopril (SQ14,225) on hemodynamics and circulating blood volume in SHR.

Koike¹,

Ito²,

Miyamoto³

et al. 1980

Hypertension

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SUMMARY Male spontaneously hypertensive rats (SHR), 13 weeks old, received oral administration of captopril (SQ 14,225) daily at a dose of 10 mg/kg or 30 mg/kg; or water at 2 ml/kg, for 6 weeks. Captopril suppressed the development of hypertension slightly at the lower dose and completely at the higher dose. At 6 weeks of dosing, hemodynamlc parameters were measured by the tracer microspbere method and blood volume by the dilution method using M Cr erythrocytes. Cardiac output (CO) increased and mean blood pressure decreased in a dose-dependent manner; thus, total peripheral resistance decreased. Cerebral and renal blood flows increased in a dose-dependent manner while blood flow to other organs tended to increase or remained unchanged. There was no significant difference in the circulating blood volume among the three groups. In conclusion, long-term blockade of angiotensin converting enzyme (ACE) with captopril dilated blood vessels in the whole body, especially in the brain and kidney, and lowered blood pressure without causing plasma expansion or tachycardia.

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“…50 Bradykinin, a potent vasodilator, has been reported to release prostaglandins from the kidney" and blood vessels,"-M and in higher doses has stimulated catecholamine release from the adrenal medulla." Enhancement of the hypotensive effect of bradykinin has been reported in conscious rabbits 28 ' ** by the administration of captopril. Thus, either bradykinin or prostaglandins of renal or vascular origin may contribute to the BP reduction seen in patients treated with captopril.…”

Section: Discussionmentioning

confidence: 98%

“…In 1977, Ondetti and coworkers" synthesized an orally active agent, captopril (SQ 14,225), which competitively inhibited angiotensin converting enzyme without acting as a substrate. Captopril has been found effective in reducing arterial hypertension in rats,"-" rabbits, 28 ' w dogs, 80 cats,' 1 and man."" The following is a report of our experience with 29 consecutively treated hypertensive patients who have been treated by inhibition of angiotensin converting enzyme by captopril.…”

mentioning

confidence: 99%

Acute and chronic effect of captropril in hypertensive patients.

Johns¹,

Baker²,

Ayers³

et al. 1980

Hypertension

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SUMMARY Acute and chronic antihypertenslve effects of the angiotensin conferring enzyme inhibitor, captoprii (SQ 14,225), was assessed in 29 consecutirely-studled patients with hypertension. (Mean arterial pressure, 110-160 mm Hg). Eighteen patients had essential hypertension (three with high plasma renln activity (PRA), 11 with normal PRA, four with low PRA); eight had renovascular hypertension (four with high PRA and four with normal PRA); two had end-stage renal parenchyma! disease, and one had primary aldosteronism due to bilateral adrenal hyperplasia. Antihypertensive drugs were discontinued approximately 1 month prior to being studied. Patients were studied on the metabolic unit and received a constant 100 mEq sodium and 60 mEq potassium/day diet Control data were obtained for 3 days with placebo treatment Captoprii was then begun at 10 or 25 mg and increased to a maximum of 100 or 150 mg four times per day. During die first 3-10 days of treatment, 16 patients (55%) achieved normal blood pressure (BP) on captoprii alone, and six patients (21%) achieved it with the addition of a diuretic Six patients (21%) exhibited a fall In diastoiic blood pressure (DBP) greater than 10 mm Hg, but did reach normal. Captoprii was ineffective in lowering BP in one patient (low PRA, essential hypertension). Of the 22 patients who achieved normal BP, all but one (normal PRA) exhibited a rise in PRA, and all exhibited a fall in plasma aldosterone concentration (PAC). Blood pressure, PRA, and PAC responses were independent of either etiologic classification or renln subtype. The mean effective daily dose of captoprii was 261 mg. Nineteen patients were followed from 1-18 months on maintenance captoprii therapy. Blood pressure remained well controlled, without evidence of toxldty, in all patients, although medication adjustment (either a dose increase or a diuretic) was required in all but five patients by the fifth outpatient month. The PRA remained elevated in 12 patients up to 6 months after discharge. The BP response was not predicted by control PRA, PAC, or BP, although there was a correlation between acute renin rise and BP reduction. These results indicate that captoprii is an effective, well-tolerated agent for the longterm treatment of hypertension of multiple etiologies. These results are consistent with captopril's known ability to block angiotensin II formation and perhaps to prevent bradyklnin degradation, although the primary mechanism responsible for BP reduction remains to be elucidated. A s S c i S r i S a " Established I n v e s t l « a t o r of the A m e n c a n H e a r t substrate has been reported with antirenin antibody/

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Inhibition of angiotensin converting enzyme by SQ 14,225 in conscious rabbits

Cited by 101 publications

References 17 publications

Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition.

Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition.

Effects of long-term blockade of angiotensin converting enzyme with captopril (SQ14,225) on hemodynamics and circulating blood volume in SHR.

Acute and chronic effect of captropril in hypertensive patients.

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