| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
Excitatory mechanisms of central sympathetic outflow by interleukin-1 beta (IL-1 beta) was investigated in urethane-anesthetized rats. intracerebroventricular administration of IL-1 beta (50-200ng/animal) elevated plasma levels of noradrenaline (NA), while those of adrenaline (Ad) were not affected. This IL-1 beta-induced elevation of NA was abolished by chemical sympathectomy, indomethacin (i.c.v.), L-N^G-nitroarginine methyl ester (i.c.v.), a nitric oxide synthase inhibitor and oxyhemoglobin (i.c.v.), a nitric oxide scavenger. D-Isomer of L-N^G-nitroarginine and methemoglobin were without effect.
Then, in the next series, roles of nitric oxide in the central excitatory mechanisms of sympatho-adrenomedullarly outflow were examined. Intracerebroventricular administration of 3-morpholinosydnominine (SIN-1), a nitric oxide doner, dose-dependently (100-500ug/animal) elevated plasma Ad and NA levels. The elevation of Ad was much more marked than that of NA.These elevations were abolished by indomethacin and carboxy-PTIO,a nitric oxide scavenger. Furthermore, the elevation of Ad levels was abolished by thromboxane A2 synthase inhibitors (furegrelate and carboxyheptyl imidazole), and also by thromboxane A2 receptor blockers ({+}-S-145 and SQ29548), while the elevation of NA was anaffected by any of these test agents.
{Conclusion} : (1) Nitric oxide mediates the IL-1beta-induced central activation of sympathetic outflow. (2) Thromboxane A2 is probably involved in the nitric oxide-induced central activation of adrenomedullary outflow.
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