l-Glutamate Evokes the Release of an Endothelium-Derived Relaxing Factor-Like Substance from the Rat Nucleus Tractus Solitarius

Summary: The purpose of the present investigations was to test the possible involvement of nitric oxide (NO) in glutamate-induced baroreceptor reflex-like responses in the rat nucleus tractus solitarius (NTS). Anesthetized normotensive rats were prepared for stereotaxic implantation of cannulae in the NTS. Blood pressure (BP) was recorded from the carotid artery. Microinjections of l-glutamate (10-1,000 nmol) into the NTS produced a dosedependent decrease in diastolic BP (DBP) and heart rate (HR). In contrast, l-glutamate had no effect when injected i.c.v. or into non-NTS sites. The cardiovascular effects of l-glutamate were abolished by the selective N-methyl-D-aspartate (NMDA) receptor agonist 2-amino-7-phosphonoheptanoic acid (2-APH). Both methylene blue (MB, an inhibitor of soluble guanylate cyclase) and NG-monomethyl-l-arginine (l-NMMA, which inhibits the production of NO) significantly reduced depressor but not bradycardic responses elicited by l-glutamate. On their own, both compounds had no effect on either DBP or HR. The results of this study demonstrate that l-glutamate microinjected into the NTS elicits a baroreceptor reflexlike response upon activation of NMDA receptors. In addition, the data with MB and l-NMMA indicate that l-glutamate induces the release of a factor with similar properties to endothelium-derived relaxing factor (EDRF)/NO, which contributes to the modulation of cardiovascular function through the NTS.