N-Methyl-D-aspartate receptor-mediated signaling in the supraoptic nucleus involves activation of a nitric...

N-Methyl-D-aspartate (NMDA) microinjection (1 mM, 0.2 microliter) into the hypothalamic supraoptic nucleus (SON) stimulated heart rate in urethane-anaesthetized rats. This effect was inhibited by coinjection of a competitive blocker of NMDA receptors, CPP (20 nmol) or by pretreatment with a sympathetic ganglionic blocker, chlorisondamine chloride (5 mg/kg i.p.), but not by prior hypophysectomy. Furthermore, the cardioexcitatory effect of intra-SON NMDA was inhibited by prior intra-SON injection of a competitive blocker of nitric oxide (NO) synthesis, NG-nitro-L-arginine methyl ester (40 nmol) or a blocker of the soluble guanylate cyclase, Methylene blue (20 nmol), and was mimicked by intra-SON injection of a calcium ionophore, A23187 (10 nmol), which stimulates NO production by raising intracellular free calcium levels. Finally, intra-SON microinjection of a membrane-permeating cGMP analog, 8-bromo-cGMP (20 nmol) stimulated heart rate in urethane-anaesthetized rats. The results point to a functional link between a sympathetically mediated cardiophysiological effect of NMDA receptor stimulation in the SON and activation of the NO/cGMP signal transduction pathway.