Local generation of angiotensin II as a mechanism of aldosterone secretion in rat adrenal capsules.
Angiotensin-converting enzyme (ACE) is found in the adrenal gland, but the role of adrenal ACE in the formation of angiotensin II (AII) and subsequent stimulation of aldosterone is unclear. We examined the effect of adrenal ACE activity on aldosterone secretion by superfusing rat adrenal capsules with angiotensin I (AI) in the presence and absence of the ACE inhibitor, lisinopril. Angiotensin I (10 microM) stimulated aldosterone secretion from 914 +/- 41 to 1465 +/- 118 pg/min/capsule (P less than 0.05). Simultaneous superfusion of AI plus lisinopril (100 microM) inhibited the stimulation of aldosterone by 73% (P less than 0.05). Perfusion of the capsules with angiotensin II (1 microM) stimulated aldosterone from 893 +/- 180 to 1466 +/- 181 pg/min/capsule (P less than 0.01). In contrast, simultaneous superfusion of AII plus lisinopril (100 microM) did not inhibit the AII stimulation of aldosterone. The failure of lisinopril to inhibit AII stimulation of aldosterone argues against a toxic or nonspecific action of lisinopril. The inhibition of AI stimulation of aldosterone release by lisinopril is mostly due to lisinopril inhibition of ACE and resulting decreased conversion of AI to AII. These results demonstrate that adrenal ACE may generate AII from AI in the adrenal gland, and this locally produce AII stimulates aldosterone.
Oda
H
H
Department of Medicine, Medical College of Ohio, Toledo 43699.
Lotshaw
D P
DP
Franco-Saenz
R
R
Mulrow
P J
PJ
D000311:Adrenal Glands / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D000450:Aldosterone; D004656:Enalapril; D000803:Angiotensin I; D002216:Captopril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A