Inducible nitric oxide synthase is involved in corticotropin-releasing hormone-mediated central sympatho-adrenal outflow in rats

Abstract

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 [Eur. J. Pharmacol. 419 (2001) 183]. 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 ω-nitro- l-arginine methyl ester (a non-selective inhibitor of NOS) [111 nmol (30 μg)/animal, i.c.v.], but not by the same dose of N ω-nitro- d-arginine methyl ester (an inactive isomer of N ω-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 μg)/animal, i.c.v.] or by S-methylisothiourea (an inhibitor of inducible NOS) [71 nmol (20 μg) and 711 nmol (200 μg)/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.