Brain converting enzyme inhibition: a possible mechanism for the antihypertensive action of captopril in spontaneously hypertensive rats.
The effects of various doses of the converting enzyme inhibitor captopril injected into the lateral brain ventricle (i.c.v.) and intravenously (i.v.) on blood pressure (BP) and on converting enzyme activity were tested in stroke prone conscious spontaneously hypertensive rats (SHR-sp) and in normotensive Wistar Kyoto rats (WKY). Injection of 500 micrograms captopril i.c.v. produced a marked biphasic BP effect in SHR-sp, an initial increase followed by a long-lasting decrease. Only the initial BP increase was observed in WKY. The pressor responses to i.c.v. angiotensin I (ANG I) were completely blocked after i.c.v. captopril injection and this effect lasted for 24 h. The pressor responses to i.v. ANG I were also inhibited immediately after 500 micrograms captopril i.c.v. and gradually returned to control values within 5 h. Intravenous injections of 500 micrograms captopril almost completely inhibited the pressor responses to i.v. ANG I; they caused a moderate BP decrease in SHR-sp and had no significant BP effects in WKY. In SHR-sp, 5 micrograms captopril i.c.v. caused a reduction of BP with a concomitant inhibition of the pressor effects of i.c.v. ANG I. Both effects lasted about 30 min. The pressor responses to i.v. ANG I were not inhibited. In WKY, 5 micrograms captopril i.c.v. had no effect on BP. It is concluded that captopril can reduce BP by action on the brain without peripheral inhibition of converting enzymes. Following high doses injected i.c.v., the inhibitor leaks into the periphery but this cannot explain the marked hypotensive effect in SHR-sp.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000201:enzymology*; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000201:enzymology*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D009994:Osmolar Concentration; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D011392:Proline; D002216:Captopril