Comparative effects of enalapril, enalaprilic acid and captopril in blocking angiotensin I-induced pressor and dipsogenic responses in spontaneously hypertensive rats.
The role of central angiotensin converting enzyme (ACE), in the maintenance of high blood pressure, was examined in unanesthetized spontaneously hypertensive rats (SHR). Pressor and dipsogenic responses induced by intracerebroventricular (ICV) injections of angiotensin I (AI) were elicited before and 30 min after either captopril (120-800 nanomoles ICV), enalapril (66-460 nanomoles ICV) and enalaprilic acid (70-280 nanomoles ICV). Enalapril was 1.6 (0.7-3.9) and 1.7 (0.9-2.9) times more potent than captopril in inhibiting AI-induced pressor and dipsogenic responses, respectively. Enalaprilic acid was 2.7 (1.1-7.1) and 2.9 (1.9-4.8) times more potent than captopril in inhibiting AI- (ICV administration) induced pressor and dipsogenic responses, respectively. None of the ACE inhibitors, in contrast, reduced the central actions of AII. Basal mean arterial pressure was not reduced by these ACE inhibitors after ICV administration. Administered orally at doses which produced similar hypotensive responses, neither captopril (30 mg/kg) nor enalapril (3 mg/kg) blocked the responses induced by AI given ICV (10 ng). These findings indicate that ACE inhibitors given acutely do not penetrate into the central nervous system sufficiently to block the dipsogenic and pressor responses induced by AI given ICV, and suggest that inhibition of central ACE may not be important to the acute antihypertensive activity of the ACE inhibitors tested.
D000803:Angiotensin I / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000809:Angiotensins / Q000037:antagonists & inhibitors*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D004151:Dipeptides / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004656:Enalapril; D015773:Enalaprilat; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D011311:Pressoreceptors / Q000187:drug effects*; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System / Q000187:drug effects; D013894:Thirst / Q000187:drug effects*; D013997:Time Factors
D000809:Angiotensins; D000959:Antihypertensive Agents; D004151:Dipeptides; D004656:Enalapril; D000803:Angiotensin I; D011392:Proline; D002216:Captopril; D015773:Enalaprilat