Nitric oxide limits pressor responses to sympathetic activation in rat spinal cord

N-methyl D-aspartate (NMDA) receptor stimulation is known to activate nitri c oxide (NO) synthase, an enzyme present in a high proportion of sympatheti c preganglionic neurons. In this study, we have examined the possibility th at NO modulates the presser responses elicited by NMDA receptor stimulation in the spinal cord. In experiments on anesthetized rats, we determined whe ther intrathecal administration of either 3-morpholinylsydnoneimine chlorid e (SIN-1), an NO donor, or N-G-nitro-L-arginine methyl ester (L-NAME), an N O synthase inhibitor, affected the response to stimulation of spinal NMDA r eceptors by NMDA (1 pmol to 1 mu mol in 10-muL intrathecal administration). Intrathecal NMDA resulted in dose-dependent increases in blood pressure. S IN-1 (100 nmol) attenuated the presser responses to NMDA (F-1,F-70 = 12, P= 0.001), Conversely, L-NAME (1 nmol to 1 mu mol) augmented the presser respo nse to NMDA in a dose-dependent manner (F-3,F-161 = 28.3, P<0.001). The eff ect of L-NAME to amplify the presser response to NMDA was reversed by L-arg inine but not by D-arginine. These results indicate that endogenous synthes is of NO in the spinal cord limits the presser response to stimulation of s pinal NMDA receptors.