Inhibition of induced aldosterone biosynthesis with a specific antagonist of angiotensin II.
The present study determined the effect of [Sar(1)-Ile(8)]-angiotensin II on steroidogenesis and induced aldosterone synthesis by the octapeptide angiotensin II, the heptapeptide des-Asp(1)-angiotensin II, and adrenocorticotropic hormone. Rabbit adrenal cells were suspended by incubation of the capsular cortical tissue with collagenase, and aldosterone levels were determined by immunoassay. Steroidogenic responses to angiotensin II and des-Asp(1)-angiotensin were essentially the same. [Sar(1)-Ile(8)]-angiotensin II (10(-7) to 5 x 10(-7) M) had no significant effect on basal aldosterone biosynthesis. However, when added with steroidogenic peptides, it completely blocked the effect of angiotensin II and des-Asp(1)-angiotensin II but not of adrenocorticotropic hormone. The dose ratio of the antagonist to angiotensin II that gave 100% inhibition was about 2:1 and to des-Asp(1)-angiotensin II, about 50:1. The data suggest that des-Asp(1)-angiotensin II has a much higher affinity for the angiotensin receptor in adrenal cortex than angiotensin II.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000032:analysis / Q000096:biosynthesis*; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D003864:Depression, Chemical; D066298:In Vitro Techniques; D007532:Isoleucine / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D011863:Radioimmunoassay; D012521:Sarcosine / Q000494:pharmacology; D014316:Tritium
D007532:Isoleucine; D014316:Tritium; D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012521:Sarcosine