A novel orally active converting-enzyme inhibitor YS 980: effects on blood pressure in spontaneously hypertensive rats.
1. The effects of long-term treatment with the angiotensin I converting-enzyme inhibitor YS 980 were examined in stroke-prone spontaneously hypertensive (sp-SH) rats. Development of hypertension was markedly blunted in the YS 980-treated animals. 2. Effective converting-enzyme inhibition was confirmed by significant increases in plasma angiotensin I (ANG I) and plasma renin concentration, inhibition of the pressor responses to intravenous ANG I and potentiation of the depressor responses to intravenous bradykinin. 3. Urinary free aldosterone excretion was decreased but no changes in urinary sodium and potassium excretion were observed. 4. The pressor responses to intravenous leucine-enkephalin were reduced. 5. The pressor responses to injection of ANG I and bradykinin into the lateral brain ventricle were unaltered. 6. We conclude that the antihypertensive action of YS 980 in sp-SH rats cannot be explained by the inhibition of the plasma renin-angiotensin system alone. Effects on other peptide systems must be considered.
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000450:Aldosterone / Q000097:blood; D000803:Angiotensin I / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology; D004743:Enkephalin, Leucine; D004745:Enkephalins / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007610:Kallikreins / Q000652:urine; D007705:Kinins / Q000378:metabolism; D008297:Male; D051381:Rats; D012083:Renin / Q000097:blood; D013438:Sulfhydryl Compounds; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D000806:Angiotensin-Converting Enzyme Inhibitors; D004745:Enkephalins; D007705:Kinins; D013438:Sulfhydryl Compounds; D013844:Thiazoles; D053778:Thiazolidines; D000450:Aldosterone; D004743:Enkephalin, Leucine; C019135:(4R)-3-((2S)-3-mercapto-2-methylpropanoyl)-4- thiazolidinecarboxylic acid; D000803:Angiotensin I; D015097:3-Mercaptopropionic Acid; D007610:Kallikreins; D012083:Renin; D001920:Bradykinin