Specific inhibition of renin by an angiotensinogen analog: studies in sodium depletion and renin-dependent hypertension.
The angiotensin substrate analog Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys has no significant effect on blood pressure in sodium-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 five studies in sodium-depleted monkeys, an infusion of 2 mg of the peptide per 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 per 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 per 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 now be applied to a wide variety of physiologic studies.
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000808:Angiotensinogen; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D008252:Macaca fascicularis / Q000502:physiology; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012083:Renin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013722:Teprotide / Q000494:pharmacology; D000092502:Renin Inhibitors
D000803:Angiotensin I; D000804:Angiotensin II; D000808:Angiotensinogen; D009842:Oligopeptides; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D012964:Sodium; D013722:Teprotide; D000092502:Renin Inhibitors; C027509:renin inhibitory peptide