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.