Specific inhibition of renin by an angiotensinogen analog: studies in sodium depletion and renin-dependent hypertension.

Abstract

The angiotensin substrate analog Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys has no significant effect on blood pressure in Na replete monkeys (Macaca fascicularis) but blocks the pressor response to infused human renin. Pressor responses to angiotensin I and angiotensin II are not attenuated. In 5 studies in Na-depleted monkeys, an infusion of 2 mg of the peptide/kg of body weight resulted in a reduction of mean arterial pressure (MAP) from 105 .+-. 4 to 79 .+-. 3 mm Hg, which is not significantly different from the response to 1 mg of the angiotensin I-converting enzyme inhibitor teprotide/kg. In uninephrectomized monkeys inflation of a suprarenal aortic cuff caused an increase in MAP from 107 .+-. 3 to 131 .+-. 3 mm Hg. Infusion of 0.6 mg of the renin-inhibitory peptide/kg was followed by a return of blood pressure to 107 .+-. 4 mm Hg: a depressor response similar to that observed with teprotide. This specific in vivo inhibitor of renin can be applied to a wide variety of physiologic studies.