Mechanisms of captopril-induced potentiation of the depressor responses to arachidonic acid in rats.
The mechanisms underlying potentiation by captopril of the depressor responses to arachidonic acid were studied in chloralose-anaesthetized rats. Captopril, in a dose (0.5 mg/kg, i.v.) which inhibited the pressor responses to angiotensin I (0.03-1 microgram/kg, i.v.), enhanced the depressor responses to bradykinin (3-300 micrograms/kg, i.v.) and potentiated the hypotensive action of arachidonic acid (3 mg/kg, intravenously). This phenomenon was observed not only when captopril and arachidonic acid were administered intravenously, but also when these compounds were injected directly into the aortic arch. The enhancement of arachidonic acid-induced hypotension by captopril was not significantly affected by pretreatment with a low dose of aprotinin (3 mg/kg, i.v.), but was abolished by bilateral nephrectomy or by pretreatment with a higher dose of aprotinin (6 mg/kg, i.v.). It is suggested that captopril augments the depressor responses to arachidonic acid by inhibiting angiotensin converting enzyme. This results in accumulation of bradykinin which in turn increases release of vasodilator prostaglandins, originating most probably, from the kidneys. The possibility that blockade of angiotensin II formation by captopril may leave the vasodilator action of prostaglandin unopposed cannot be excluded.
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Hui
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Dai
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Ogle
D000803:Angiotensin I / Q000008:administration & dosage; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D007611:Aprotinin / Q000008:administration & dosage; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000008:administration & dosage; D002216:Captopril / Q000008:administration & dosage*; D004357:Drug Synergism; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D001095:Arachidonic Acids; D016718:Arachidonic Acid; D000803:Angiotensin I; D007611:Aprotinin; D002216:Captopril; D001920:Bradykinin