Inducible nitric oxide synthase is involved in corticotropin-releasing hormone-mediated central sympatho-adrenal outflow in rats.
Brain nitric oxide (NO), recognized as a neurotransmitter or a neuromodulator, is mainly generated either by neuronal NO synthase (NOS) or by inducible NOS. NO has been shown to activate cyclooxygenase (a prostaglandin-forming enzyme) in addition to guanylate cyclase. Recently, we reported that the intracerebroventricularly (i.c.v.) administered corticotropin-releasing hormone (CRH) increases plasma catecholamines through brain cyclooxygenase-dependent mechanisms in rats. In the present experiments, therefore, we examined whether NO is involved in the CRH-induced increase of plasma catecholamines using urethane-anesthetized rats. I.c.v. administered CRH increased plasma noradrenaline and adrenaline in a dose-dependent manner (0.5, 1.5, and 3.0 nmol/animal). The CRH (1.5 nmol/animal, i.c.v.)-induced increase of plasma catecholamines was reduced by N(omega)-nitro-L-arginine methyl ester (a non-selective inhibitor of NOS) [111 nmol (30 microg)/animal, i.c.v.], but not by the same dose of N(omega)-nitro-D-arginine methyl ester (an inactive isomer of N(omega)-nitro-L-arginine methyl ester). The CRH-induced increase of plasma catecholamines was also reduced either by cycloheximide (an inhibitor of protein synthesis) [107 nmol (30 microg)/animal, i.c.v.] or by S-methylisothiourea (an inhibitor of inducible NOS) [71 nmol (20 microg) and 711 nmol (200 microg)/animal, i.c.v.]. These results suggest the involvement of brain inducible NOS in the CRH-induced activation of the central sympatho-adrenomedullary outflow in rats.
D000313:Adrenal Medulla / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D002395:Catecholamines / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors
D002395:Catecholamines; D007527:Isoenzymes; D003346:Corticotropin-Releasing Hormone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester