Stimulation of endogenous nitric oxide production is involved in the inhibitory effect of adrenomedullin on aldosterone secretion in the rat.
Adrenomedullin (AM) (10(-8) M) partially suppressed aldosterone response of dispersed rat zona glomerulosa (ZG) cells to 10 mM K+, and the nitric oxide (NO) synthase inhibitors L-NAME (10(-3) M) and 1400W (10(-4) M) effectively counteracted this effect of AM. The NO donor L-Arginine (L-Arg) (10(-5) M) decreased both basal and K+ -stimulated aldosterone secretion. The guanylate-cyclase inhibitor Ly-83583, at a concentration (10(-4) M) abolishing either the guanylate-cyclase activator guanylin- or L-Arg-induced cGMP release from dispersed ZG cells, did not affect the aldosterone antisecretagogue action of AM and L-Arg. AM (10(-8) M) evoked a moderate increase in cGMP release by dispersed ZG cells, and the effect was blocked by both 10(-4) M Ly-83583 and 10(-3) M L-NAME. Collectively, these findings allow us (1) to confirm that NO inhibits aldosterone secretion through a cGMP-independent mechanism; and (2) to suggest that stimulation of endogenous NO synthesis plays a role in the mechanisms underlying the inhibitory effect of AM on K+ -stimulated aldosterone secretion from rat ZG cells.
Rebuffat
P
P
Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua, 35121, Padua, Italy.
Malendowicz
L K
LK
Nussdorfer
G G
GG
Mazzocchi
G
G
D053607:Adrenomedullin; D000450:Aldosterone / Q000378:metabolism* / Q000494:pharmacology; D000578:Amidines / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015384:Zona Glomerulosa / Q000378:metabolism
D000578:Amidines; D000634:Aminoquinolines; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D010455:Peptides; D053607:Adrenomedullin; D009569:Nitric Oxide; D000450:Aldosterone; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester