Nitric oxide mediates central activation of sympathetic outflow induced by interleukin-1 beta in rats.
The excitatory mechanism of central sympathetic outflow induced by interleukin-1 beta was investigated in urethane-anesthetized rats. Intracerebroventricular administration of interleukin-1 beta induced a gradually developing elevation of plasma noradrenaline levels in a dose-dependent manner (50, 100 and 200 ng/animal), while the levels of adrenaline were not affected. The elevation of noradrenaline levels induced by interleukin-1 beta (100 ng/animal i.c.v.) was abolished by the following treatments with: (1) a chemical sympathectomizer, 6-hydroxydopamine (15 mg/kg i.v., 3 days before); (2) a prostaglandin synthesis inhibitor, indomethacin (500 micrograms/animal i.c.v.); (3) a nitric oxide synthase inhibitor, L-NG-nitroarginine methyl ester (100 micrograms plus 10 micrograms/min i.c.v.); and (4) a nitric oxide scavenger, oxyhemoglobin (32.3 micrograms plus 3.23 micrograms/min i.c.v.). In contrast to these results, D-NG-nitroarginine methyl ester, an inactive isomer of L-NG-nitroarginine methyl ester, and methemoglobin, a metabolite of oxyhemoglobin, were without effect. Furthermore, prostaglandin E2 (100 ng/animal i.c.v.) rapidly and markedly elevated the plasma level of noradrenaline but not adrenaline. This prostaglandin E2-induced elevation of plasma noradrenaline levels was not attenuated by L-NG-nitroarginine methyl ester (100 micrograms plus 10 micrograms/min i.c.v.). The present results suggest that nitric oxide is involved in the interleukin-1 beta-induced central activation of sympathetic outflow. Furthermore, there probably exists nitric oxide-linked prostaglandin-generating system in the brain.
Murakami
Y
Y
Department of Pharmacology, Kochi Medical School, Japan.
Yokotani
K
K
Okuma
Y
Y
Osumi
Y
Y
D000768:Anesthesia, General; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood; D015232:Dinoprostone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000097:blood; D016627:Oxidopamine; D010108:Oxyhemoglobins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D014520:Urethane
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002395:Catecholamines; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D014520:Urethane; D016627:Oxidopamine; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin