SA446, a new orally active converting enzyme inhibitor: antihypertensive action and comparison with captopril in stroke-prone spontaneously hypersensitive rats.
The converting enzyme inhibitors (CEI) SA446 and Captopril (CAP) were given orally at a dose of 50 mg/kg per day to adult stroke-prone spontaneously hypertensive rats (SHRSP) over a period of four weeks. Both CEI lowered arterial blood pressure (BP) to a similar extent. CAP was more inhibitory on the plasma renin-angiotensin system (RAS) than SA446. Both CEI lowered urinary aldosterone excretion but had little (SA446) or no (CAP) natriuretic effect. CAP reduced the pressor responses to intravenous (i.v.) angiotensin I (ANG I) more (52%) than SA446 (18%) and potentiated the depressor responses to i.v. bradykinin more (fortyfold) than SA446 (tenfold). In contrast, SA446 treatment reduced the pressor responses to intracerebroventricular (i.c.v.) ANG I by 21% and led to a rise in the hypothalamic renin concentration. Oral CAP treatment for four weeks did not produce these signs of a brain converting enzyme inhibition. It is concluded that SA446 is equally as antihypertensive as CAP in SHRSP. SA446 appears to penetrate more readily into the brain and to exert its action partly through inhibition of the brain RAS which is known to be stimulated in SHRSP.
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000450:Aldosterone / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D007610:Kallikreins / Q000652:urine; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D012083:Renin / Q000378:metabolism; D013438:Sulfhydryl Compounds; D053778:Thiazolidines
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D013438:Sulfhydryl Compounds; D053778:Thiazolidines; D000450:Aldosterone; D011392:Proline; D002216:Captopril; D015097:3-Mercaptopropionic Acid; C033437:rentiapril; D007610:Kallikreins; D012083:Renin; D011188:Potassium