ANTIHYPERTENSIVE ACTIVITY IN RATS OF SQ 14,225, AN ORALLY ACTIVE INHIBITOR OF ANGIOTENSIN I-CONVERTING ENZYME

Abstract

SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline) marked lowered the blood pressure of the renin-dependent aortic-ligated and 2-kidney Goldblatt hypertensive rat and failed to reduce blood pressure in the 1-kidney Goldblatt hypertensive rat. In the 2-kidney Goldblatt rat, SQ 14,225 (orally) 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 2-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. SQ 14,225 may act primarily by inhibiting the renin-angiotensin system to reduce elevated blood pressure, especially in presumably renin-dependent models of hypertension.