Angiotensin II's role in mediating angiotensin I- and tetradecapeptide-induced steroidogenesis by rat glomerulosa cells.
To evaluate the role of angiotensin II (A II) in mediating the steroidogenic response to angiotensin I (A I) and tetradecapeptide, rat glomerulosa cells were incubated with each peptide in the presence or absence of an angiotensin-converting enzyme inhibitor (captopril or the nonapeptide bradykinin-potentiating factor). Both A I and tetradecapeptide increased aldosterone secretion in a dose-dependent fashion, but were considerably less effective (P less than 0.001) than the same dose (2.4 X 10(-9) M) of A II. In addition, both A I and tetradecapeptide caused a dose-dependent increase in A II accumulation in the incubation media, indicating that part of their steroidogenic effect is indirect via conversion to the octapeptide. While captopril (1.0 X 10(-4) M) almost completely blocked A I (2.4 X 10(-8) M)-induced A II accumulation, it caused only a 50% reduction (P less than 0.01) in aldosterone output. The nonapeptide-converting enzyme inhibitor (2.3 X 10(-6) M) produced a similar blockade. This lack of complete inhibition of A I-induced steroidogenesis suggests that A I also has a direct effect on the glomerulosa cells, i.e. 50% of the activity of A I is due to intrinsic activity. On the other hand, converting enzyme inhibitors did not affect tetradecapeptide-induced aldosterone output or A II accumulation, making it impossible to determine if it has a direct steroidogenic effect. The failure of converting enzyme inhibitors to modify tetradecapeptide-induced accumulation of A II suggests that an enzyme other than converting enzyme is responsible for its generation.
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000808:Angiotensinogen / Q000378:metabolism / Q000494:pharmacology*; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D051381:Rats
D000809:Angiotensins; D000808:Angiotensinogen; D000804:Angiotensin II; D000450:Aldosterone; D000803:Angiotensin I; D002216:Captopril