Roles of brain nitric oxide and prostaglandins in the regulation of central sympatho-adrenomedullary outflow in rats

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We already reported that intracerebroventricularly (i.c.v.) administered interleukin-1beta (IL-1beta) inhibits vagally activated gastric acid secretion by activation of central prostaglandin (PG)-mediated sympathetic outflow (Eur.J.Pharmacol., 1995). I.c.v. administered PGE^2 also activates central sympathetic outflow through activation of brain EP3 receptors (Br.J.Pharmacol., 1995 ; 1996). In the present experiments, we examined possible roles of central nitric oxide (NO) in IL-1beta-mediated central activation of sympathetic outflow using male Wistar rats anesthetized with urethane. (1) I.c.v.administered IL-1beta elevated plasma noradrenaline (NA) levels. This IL-1beta-mediated response was abolished by i.c.v.administered 1-NAME (NO synthase inhibitor), oxyhemoglobin (NO scavenger), and indomethacin (cyclooxygenase inhibitor), (2) I.c.v.administered NO donors, sodium nitroprusside and 3-morpholinosydnonimine (SIN-1), inhibited vagally stimulated gastric acid secretion. This response was abolished by i.c.v.administered indomethacin, splanchnectomy and intramuscularly administered phentolamine, SIN-1 elevated plasma levels of adrenaline (Ad) and NA (Ad>>NA). SIN-1-mediated elevation of Ad and NA was abolished by intracerebroventricular pretreatment with indomethacin. On the other hand, intracerebroventricular pretreatment with thromboxane A2 synthase inhibitor, furegrelate, only abolished SIN-1-induced Ad elevation. These results indicate that central NO activates central sympatho-adrenomedullary system. I.c.v.administered IL-1beta activates central sympathetic outflow through NO-PG (E2) pathway and central thromboxane A2 activates central adrenomedullary pathways.