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A Specific Competitive Antagonist of the Vascular Action of Angiotensin II

The effect of 1-Asn-8-Ala-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 1-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 norepinephtine, serotonin, and histamine were relatively unaffected. No pA3 values could be obtained with these agonists in the concentration range tested. Partial dose-response (pressor) curves for angiotensin II in pithed rats shifted to the right during infusions of 1-Asn-8-Ala-angiotensin II at 20 and 60 μg/kg min−1 Partial dose-response curves for vasopressin, phenylephririe, and tyramine were unaffected. Infusions of 1-Asn-8-Ala-angiotensin II counteracted the pressor effect of angiotensin II infusions in pithed and conscious rats. Infusions of 1-Asn-8-Ala-angiotensin II (200 μ/ kg min−1) 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 with acute unilateral renal hypertension. The data presented are consistent with the conclusion that 1-Asn-8-Ala-angiotensin II is a specific competitive antagonist of the vascular action of angiotensin II both in vitro and in vivo.