Centrally applied nitric oxide donor elevates plasma corticosterone by activation of the hypothalamic noradrenergic neurons in rats

Abstract

The present study was undertaken to investigate the mechanisms involved in a nitric oxide donor [3-morpholino-sydnonimine (SIN-1)]-induced activation of hypothalamic–pituitary–adrenal axis in urethane- and α-chloralose-anesthetized rats. Intracerebroventricularly (i.c.v.) administered SIN-1 (250 and 500 μg/animal) effectively and dose-dependently elevated plasma levels of corticosterone. Pretreatment with phentolamine (250 μg/animal, i.c.v.), an α-adrenoceptor antagonist, attenuated the elevation of plasma corticosterone evoked by SIN-1, but sotalol (300 μg/animal, i.c.v.), a β-adrenoceptor antagonist, was without effects. The same doses of SIN-1 also increased the release of noradrenaline in the hypothalamic paraventricular nucleus (PVN) measuring microdialysis technique, and this increase was abolished by tetrodotoxin (1 μM) administered into the perfusion solution of the PVN. Furthermore, pretreatment with indomethacin (500 μg/animal, i.c.v.), a cyclooxygenase inhibitor, abolished the SIN-1-induced elevations of both noradrenaline in the PVN and plasma corticosterone. These results suggest that i.c.v. administered SIN-1 activates central noradrenergic neurons innervating the PVN by prostaglandin-mediated mechanisms. Released noradrenaline in the PVN elevates plasma levels of corticosterone via an activation of the central α-adrenoreceptors in rats.