Evidence for Different Angiotensin II Receptors in Rat Adrenal Glomerulosa and Rabbit Vascular Smooth Muscle Cells
Studies with Competitive Antagonists
Angiotensin II (AII) acts as both an endogenous vasoconstrictor agent and a specific trophic hormone that controls aldosterone secretion. The characteristics of vascular and adrenal receptors for AII were examined in vitro by comparing stimulation and blockade induced by two structural analogues of AII. The adrenal response was assessed on the basis of corticosterone and aldosterone production by isolated rat glomerulosa cells; isolated rabbit aortic strips provided an index of the response of vascular smooth muscle. Threshold sensitivity to AII in both tissues was 0.3-1.0 ng/ml with a peak response at about 300 ng/ml. PII3 (I-Sar-8-Ala-AII) was a competitive antagonist in both systems; 1-10 ng/ml of PII3 produced a significant parallel shift of the All dose-response curve (P < 0.01). The maximum response was not reduced; increasing doses of AII overcame the blockade, and the responses to other agonists were not influenced. PII3 did not stimulate either tissue. P4T8 (4-Phe-8-Tyr-AII) was a partial agonist in the rabbit aorta; 100 ng/ml of P4T8 induced competitive blockade, and contraction followed doses above 1,000 ng/ ml. Conversely, P4T8 neither stimulated nor blocked the adrenal receptors, despite very high concentrations. Thus, the results of this study reveal functional differences in the All receptors in the two systems and provide an approach to designing therapeutic agents that might block only one of its two major biological effects.
- aldosterone secretion
- vascular reactivity
- 1-Sar-8-Ala-angiotensin II
- 4-Phe-8-Tyr-angiotensin II
- angiotensin analogues
- Received November 26, 1973.
- Accepted January 2, 1974.
- © 1974 American Heart Association, Inc.