Effect of neurogenic stress and ethanol on nitric oxide synthase and cyclooxygenase activities in rat adrenals.
Repeated restraint stress (RRS) in male rats activated the pituitary adrenal system, as indicated by increases in adrenal weight and plasma corticosterone concentration that were accompanied by a decrease in constitutive nitric oxide synthase (cNOS), but not inducible NOS (iNOS). iNOS activated cyclooxgenase, causing elevated prostaglandin E(2) (PGE(2)) and F(2 alpha) in the adrenals, but had no effect on lipoxygenase. Administration of ethanol (ETOH) was also associated with elevated adrenal weight and a slight increase in corticosterone coupled with a decrease in both cNOS and iNOS and PGs in the adrenal. When ETOH was administered together with RRS, a decrease in iNOS and PGE release was noted consequent to a reduction in iNOS. Thus, ETOH probably reduced RRS-induced adrenocorticotropic hormone release. Adrenals were incubated in vitro to further evaluate the role of NO in these processes. Results indicated that NO released by sodium nitroprusside increased corticosterone release presumably by activating guanylyl cyclase with production of cyclic guanosine monophosphate (cGMP), because although NO also increased PGE release, PGE(2) (10(-5)-10(-9) M) decreased corticosterone release, an effect that was highly significant at a concentration of 10(-7) M PGE(2). ETOH (100 mM) had no effect on corticosterone release and did not block the increase in corticosterone caused by NO; however, ETOH reduced PGE release into the medium and blocked PGE(2) release induced by NO. Consequently, NO activated corticosterone release not by PGs, but by activation of guanylyl cyclase and release of cGMP. PGs have a negative feedback to suppress corticosterone release.
Rettori
Valeria
V
Centro de Estudios Farmacologicos y Botanicos (CEFYBO-CONICET), Serrano 669, 1414 Buenos Aires, Argentina.
Mohn
Claudia
C
Scorticati
Camila
C
Vissio
Paula
P
Cella
Maximiliano
M
Farina
Mariana
M
Franchi
Ana
A
McCann
Samuel M
SM
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*
D015777:Eicosanoids; D000431:Ethanol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D003345:Corticosterone