Nitric oxide inhibits human aldosteronogenesis without guanylyl cyclase stimulation.
Deta nonoate (deta-NO), a zwitterion nitric oxide (NO) donor, potently inhibited forskolin- and angiotensin II-stimulated aldosterone production in human adrenocortical H295R cells in a concentration-dependent manner (0.1-1000 microM). The half-maximal and maximal inhibition of forskolin-evoked aldosteronogenesis occurred at 0.6 and 100 microM deta-NO, respectively. The respective half-maximal and maximal deta-NO-mediated inhibition of angiotensin II-stimulated aldosterone generation occurred at 150 microM and 1 mM. In H295R cells, deta-NO and sodium nitroprusside did not stimulate cGMP production, and the soluble guanylyl cyclase inhibitor oxadiazoloquinoxalinone (10 microM) did not block deta-NO-mediated attenuation of aldosteronogenesis. 25-Hydroxycholesterol (10 microM)-facilitated aldosterone synthesis was also diminished with half-maximal and maximal inhibition occurring at 120 microM and 1 mM deta-NO, respectively. Taken together, these results demonstrate that NO inhibits human aldosteronogenesis without stimulating guanylyl cyclase in H295R cells.
Kreklau
E L
EL
Department of Pharmacology and Toxicology, University of North Dakota School of Medicine and Health Sciences, Grand Forks 58202-9037, USA.
Carlson
E J
EJ
Drewett
J G
JG
D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism*; D000450:Aldosterone / Q000096:biosynthesis*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D016716:PC12 Cells; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D006888:Hydroxycholesterols; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D010069:Oxadiazoles; D011810:Quinoxalines; D000804:Angiotensin II; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009599:Nitroprusside; D005576:Colforsin; D009569:Nitric Oxide; D000450:Aldosterone; C007997:25-hydroxycholesterol; D006162:Guanylate Cyclase; D006152:Cyclic GMP