PT - JOURNAL ARTICLE AU - R J Laffan AU - M E Goldberg AU - J P High AU - T R Schaeffer AU - M H Waugh AU - B Rubin TI - Antihypertensive activity in rats for SQ 14,225, an orally active inhibitor of angiotensin I-converting enzyme. DP - 1978 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 281--288 VI - 204 IP - 2 4099 - http://jpet.aspetjournals.org/content/204/2/281.short 4100 - http://jpet.aspetjournals.org/content/204/2/281.full SO - J Pharmacol Exp Ther1978 Feb 01; 204 AB - SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline) markedly lowered the blood pressure of the renin-dependent aortic-ligated and two-kidney Goldblatt hypertensive rat and failed to reduce blood pressure in the one-kidney Goldblatt hypertensive rat. In the two-kidney Goldblatt rat, SQ 14,225 (p.o.) was about 10 times as potent as teprotide, the nonapeptide SQ 20,881 (s.c.). Oral doses of SQ 14,225 moderately reduced the blood pressure of the Wistar-Kyoto spontaneously hypertensive rat but not that of the normotensive Wistar-Kyoto rat. Bilateral nephrectomy abolished the antihypertensive activity of SQ 14,225 in the spontaneously hypertensive rat. SQ 14,225 and SQ 20,881 elicited parallel dose-response curves in the two-kidney renal hypertensive rat. Post-treatment of spontaneously hypertensive rats with either agent failed to augment the antihypertensive effect produced by effective doses of the other agent. The results suggest that SQ 14,225 acts primarily by inhibiting the renin-angiotensin system to reduce elevated blood pressure, especially in presumably renin-dependent models of hypertension.