Effects of SQ 14,225, an orally active inhibitor of angiotensin-converting enzyme on blood pressure, heart rate and plasma renin activity of conscious normotensive dogs.
Oral administration of SQ 14,225 (0.03--3 mg/kg) to conscious normotensive dogs caused inhibition of the pressor response to intravenously administered angiotensin I (AI), the duration of which was dose-dependent. All doses of 0.1 mg/kg or greater caused 85--95% inhibition 30 min after administration whereas 0.03 mg/kg produced only a 25% inhibition. Pressor responses to angiotensin II (AII) were not similarly inhibited. Blood pressure was moderately reduced in a dose-related manner and followed the same pattern as inhibition of the AI pressor responses. The maximum change occurred after 1.0 mg/kg with only a more rapid onset occurring after the 3.0 mg/kg dose. Heart rate was not appreciably changed. SQ 14,225 also increased plasma renin activity (PRA), the levels and duration of which were dose-related. These data indicate that SQ 14,225 is an orally effective, potent inhibitor of angiotensin I-converting enzyme (ACE) in dogs. It appears that in mongrel dogs, ACE inhibition results in a slight to moderate reduction in blood pressure and an increase in PRA.
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012083:Renin / Q000097:blood*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D011392:Proline; D012083:Renin