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  • Title: Clinical pharmacology of angiotensin antagonists.
    Author: Pettinger WA, Mitchell HC.
    Journal: Fed Proc; 1976 Nov; 35(13):2521-5. PubMed ID: 976494.
    Abstract:
    The early clinical pharmacologic investigations of saralasin were facilitated by the availability of a highly sensitive and specific radioimmunoassay for this peptide. In these studies, plasma concentrations of saralasin were correlated with inhibition of angiotensin receptors in each of three organ systems: vascular smooth muscle, adrenal cortex, and the renin release control mechanism in the kidney. The biochemical half-life of plasma saralasin was 3.2 min and an infusion time-to-plateau was 12--15 min. Saralasin inhibited adrenal cortical, vascular, and intrarenal (renin release) angiotensin receptors. The time required for manifesting these blocking actions was short(3--10 min) except for the 30--60 min required to suppress plasma aldosterone. Saralasin-induced blood pressure lowering was dependent on previously elevated serum renin activity and volume depletion. Expansion of intravascular volume prevented hypotensive responses to saralasin even in high-renin patients. Saralasin-induced renin release occurred independent of hypotension and could be inhibited by propranolol, a beta-adrenergic blocking agent. Thus, saralasin is a selective angiotensin antagonist which lacks organ specificity. It is a highly useful tool in pharmacologic studies of the renin--angiotensin axis in man and shows promise as a diagnostic tool.
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