Effects of nitric oxide on aldosterone synthesis and nitric oxide synthase activity in glomerulosa cells from bovine adrenal gland.
This study investigated the effects of two NO-releasing agents, diethylenetriamine-NO (deta-NO) and sodium nitroprusside (SNP), on basal, ACTH-, and angiotensin II (AngII)-stimulated aldosterone production in glomerulosa cells from bovine adrenal gland. NO donors inhibited basal and ACTH- or AngII-stimulated aldosterone synthesis in a concentration-dependent manner. Deta-NO and SNP also provoked a concentration-dependent stimulation of cGMP production. However, cGMP was not responsible for the inhibition of aldosterone secretion, because a cGMP analog did not reproduce the inhibitory effect. Moreover, soluble guanylyl cyclase or protein kinase G inhibitors did not revert the inhibitory effect of NO on aldosterone production. NO donors did not modify ACTH-stimulated cAMP production or AngII-stimulated PLC activity stimulation, but inhibited 22[R] hydroxycholesterol- or pregnenolone-stimulated aldosteronogenesis. NO can be synthesized in bovine glomerulosa cells because nitrite production was determined and characterization of NOS activity was also performed. Nitrite accumulation was not modified in the presence of ACTH, AngII, or other factors used to induce iNOS. NOS activity that showed a Michaelis-Menten kinetic was NADPH- and calcium-dependent and was inhibited by two competitive inhibitors, L-NAME and L-NMMA. These results show that NO inhibits aldosterone production in glomerulosa cells acting on P450scc and other P450-dependent steroidogenic enzymes, and these cells display NOS activity suggesting that NO can be produced by constitutive NOS isozymes.
Sainz
José M
JM
Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country/Euskal Herriko Unibertsitatea, Box 644, 48080-Bilbao, Spain.
Reche
Cecilia
C
Rábano
María A
MA
Mondillo
Carolina
C
Patrignani
Zoraida J
ZJ
Macarulla
José M
JM
Pignataro
Omar P
OP
Trueba
Miguel
M
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis*; D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002457:Cell Extracts; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005003:Ethisterone / Q000494:pharmacology; D006162:Guanylate Cyclase; D006888:Hydroxycholesterols / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009599:Nitroprusside / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D000071756:Soluble Guanylyl Cyclase; D015384:Zona Glomerulosa / Q000187:drug effects* / Q000201:enzymology; D019323:omega-N-Methylarginine / Q000037:antagonists & inhibitors
D000809:Angiotensins; D002457:Cell Extracts; D004791:Enzyme Inhibitors; D006888:Hydroxycholesterols; D020030:Nitric Oxide Donors; D011073:Polyamines; D018160:Receptors, Cytoplasmic and Nuclear; C005391:diethylenetriamine; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP; D005003:Ethisterone; D019331:NG-Nitroarginine Methyl Ester