Pharmacological manipulation of central nitric oxide/guanylate cyclase activity alters Fos expression by rat hypothalamic vasopressinergic neurons during acute glucose deprivation

Neurohypophyseal secretion of arginine vasopressin is stimulated by decreas ed systemic glucose availability. Nitric oxide is produced by paraventricul ar and supraoptic magnocellular neurons, and is implicated in central mecha nisms controlling plasma vasopressin and glucose levels. The current studie s investigated the role of this neurotransmitter in glucoprivic induction o f AP-1 transcriptional activity in hypothalamic vasopressinergic neurons by examining whether pharmacological manipulation of central nitric oxide/gua nylate cyclase/cGMP signaling alters nuclear accumulation of Fos immunoreac tivity in these cells. Adult male rats pretreated by intraventricular admin istration of saline exhibited extensive colabeling of vasopressinergic neur ons in both brain sites for Fos following systemic injection of the glucose antimetabolite, 2-deoxy-D-glucose. Pretreatment with the nitric oxide dono r, SIN1, resulted in decreased numbers of paraventricular and supraoptic Fo s-positive vasopressinergic neurons during glucoprivation. In other animals , coadministration of SIN1 and the nitric-oxide sensitive guanylate cyclase inhibitor, ODQ, prior to the antimetabolite reversed these inhibitory effe cts of SIN1 on Fos expression by these cells. Intracerebral administration of ODQ alone did not significantly enhance expression of Fos by vasopressin ergic neurons in either site. The present studies demonstrate that exogenou s activation of the nitric oxide/guanylate cyclase/cGMP pathway in the brai n inhibits nuclear accumulation of the AP-1 transcription factor, Fos, in v asopressinergic neurons during cellular glucopenia, and suggest that this n eurotransmitter is critical for transactivational effects of glucoprivation on these neuropeptidergic neurons. (C) 1999 Elsevier Science B.V. All righ ts reserved.