Brain inducible nitric oxide synthase is involved in interleukin-1beta-induced activation of the central sympathetic outflow in rats.
Nitric oxide (NO) has been recognized as a neurotransmitter or a neuromodulator in the central nervous system. Brain NO is mainly generated either by neuronal NO synthase (NOS) or by inducible NOS. Previously we reported that central NO is involved in the elevation of plasma noradrenaline levels induced by intracerebroventricularly (i.c.v.) administered interleukin-1beta in rats [Eur. J. Phamacol. 317 (1996) 61]. In the present study, therefore, we tried to characterize which type of NOS isoforms is involved in the cytokine-induced responses using selective inhibitors of each NOS isoform in urethane-anesthetized rats. I.c.v. administered interleukin-1beta (100 ng/animal) elevated plasma levels of noradrenaline but not adrenaline. The cytokine-induced elevation of plasma noradrenaline levels was attenuated by cycloheximide, an inhibitor of protein synthesis, in a dose-dependent manner (10 and 20 microg/animal, i.c.v.). S-ethylisothiourea (0.1 and 0.5 microg/animal, i.c.v.), an inhibitor of inducible NOS, dose-dependently reduced the cytokine-induced elevation of plasma noradrenaline levels, while 7-nitroindazole (5 and 10 microg/animal, i.c.v.), an inhibitor of neuronal NOS, had no effect. These results suggest the involvement of brain inducible NOS in the interleukin-1beta-induced activation of the central sympathetic outflow in rats.
Murakami
Yoshinori
Y
Department of Pharmacology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
Okada
Shoshiro
S
Yokotani
Kunihiko
K
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D004790:Enzyme Induction / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism
D007375:Interleukin-1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D009638:Norepinephrine