1. The angiotensin II antagonism by newly synthesized 8-C-phenylglycine analogues of [5-isoleucine]angiotensin II in different preparations was investigated in vitro and in vivo.
2. All analogues competitively inhibited the myotropic effect of angiotensin II on the isolated colon ascendens of the guinea-pig and the stomach of the rat.
3. In normotensive dogs, cats, rabbits, guinea-pigs and rats the blood pressure response to infused angiotensin II was inhibited by the antagonists. The angiotensin II-induced fall in renal blood flow in the dog was blocked during infusion of the analogues. Acute renal hypertension in rats was significantly decreased. Of conscious rats variously with normal blood pressures, spontaneous hypertension and chronic renal hypertension, only in the last group could a marked uniform fall in blood pressure be demonstrated. The central pressor effect of angiotensin II was also inhibited in conscious rats.
4. 8-C-Phenylglycine analogues of [5-isoleucine]-angiotensin II exhibit a specific antagonistic activity to endogenous and exogenous angiotensin II.