A specific competitive antagonist of the vascular action of angiotensin. II.

The effect of l-Asn-8-Ak-angiotensin II (Asn-Arg-Val-Tyr-Val-His-Pro-Ala) on the vascular action of angiotensin II was studied with rabbit aortic strips, pithed rats, and conscious rats. Dose-response (contraction) curves for angiotensin II on rabbit aortic strips shifted progressively to the right with increasing bath concentrations of l-Asn-8-Ala-angiotensin II. The pA2 value (an indication of the relative affinity of a competitive antagonist for an agonist's receptor site) was 6.84 ± 0.03. Dose-response curves for norepinephrine, serotonin, and histamine were relatively unaffected. No pA3 values could be obtained with these agonists in the concentration range tested. Partial doseresponse (pressor) curves for angiotensin II in pithed rats shifted to die right during infusions of l-Asn-8-Ala-angiotensin II at 20 and 60 yu,g/kg mkr. Partial dose-response curves for vasopressin, phenylephrine, and tyramine were unaffected. Infusions of l-Asn-8-Ala-angiotensin II counteracted the pressor effect of angiotensin II infusions in pithed and conscious rats. Infusions of 1Asn-8-Ala-angiotensin II (200 ̂ ig/kg min") effective in reducing the blood pressure of conscious angiotensin II-infused rats caused only small pressor effects in conscious normotensive rats but reduced the blood pressure in 75% of the conscious rats witii acute unilateral renal hypertension. The data presented are consistent with the conclusion that l-Asn-8-Ala-angiotensin II is a specific competitive antagonist of the vascular action of angiotensin II both in vitro and in vivo.