Antihypertensive activity in rats for SQ 14,225, an orally active inhibitor of angiotensin I-converting enzyme

RJ Laffan, ME Goldberg, JP High, TR Schaeffer, MH Waugh and B Rubin

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.

Volume 204, Issue 2, pp. 281-288, 02/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				T. Takabatake, H. Ohta, Y. Yamamoto, Y.-i. Ishida, H. Hara, Y. Ushiogi, S. Nakamura, and N. Hattori Effect of Angiotensin Blockade and Converting Enzyme Inhibition on Renovascular Hypertension: Comparison Between Unilateral and Bilateral Renal Artery Stenosis Angiology, June 1, 1987; 38(6): 434 - 439. [Abstract] [PDF]