Adrenal responses to pharmacological interruption of the renin-angiotensin system in sodium-restricted normal man.
We assessed the role of the renin-angiotensin system in the control of aldosterone secretion in response to sodium restriction in 62 normal subjects. Both saralasin, an angiotensin II antagonist, and SQ 20881, a converting enzyme inhibitor, induced a dose-related decrease in plasma aldosterone levels when the renin-angiotensin system was activated by restriction of sodium intake. Two types of experiments were performed with saralasin. In the first set, a dose-response relationship was established 20 min after beginning infusions ranging from 0.03-1.0 microgram/kg/min. The optimal dose was 0.1 microgram/kg/min, with a reduction in aldosterone levels of -10.1 +/- 3.8 ng/dl (P less than 0.025). Higher doses induced smaller reductions in aldosterone levels. In the second set, a 3-h infusion was given. The results were qualitatively similar but the magnitude was greater (-15 +/- 4 ng/dl; P less than 0.01). The aldosterone response 20 min after administration of SQ 20881 paralleled the angiotensin II response, with the first significant decrement (-6.5 +/- 1.5 ng/dl; P less than 0.01) occurring at 0.1 mg/kg and maximum (-10 +/- 3 ng/dl) occurring at 0.3 mg/kg. Thus, both agents produced qualitatively similar changes in aldosterone secretion in sodium-restricted normal subjects. However, neither reduced sodium restricted aldosterone levels to that measured in sodium-loaded subjects because of the intrinsic limitation of each agent. Saralasin is a partial agonist. SQ 20881 induces an increase in plasma renin activity via interruption of the short feedback loop, which probably limits its action. Yet, these data do support the hypothesis that angiotensin mediates the adrenal's response to sodium restriction in normal man.
D000293:Adolescent; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000097:blood; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008875:Middle Aged; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System; D012504:Saralasin; D013722:Teprotide
D000804:Angiotensin II; D000450:Aldosterone; D013722:Teprotide; D012083:Renin; D012504:Saralasin