POSSIBLE PARTICIPATION OF SPINAL NITRIC-OXIDE IN THE CONTROL OF THE BLOOD-PRESSURE IN ANESTHETIZED RATS

In pentobarbital-anesthetized rats the intrathecal (i.t.) injection of the nitric oxide (NO) precursor, L-arginine (10 and 20 mu mol), elici ted a decrease in the mean blood pressure (MBP) whereas the inhibitor of the NO synthase (NOS) NG-nitro-L-arginine methyl ester (L-NAME; 0.1 -10 mu mol) produced a dose-dependent presser effect. The presser resp onse to L-NAME was prevented by pretreatment with L-arginine. Neither D-arginine nor D-NAME modified the MBP. The NO donor sodium nitropruss ide (SNP; 0.125 and 0.25 mu mol, i.t.) induced a hypotensive response followed by a presser effect. The dual response to SNP as well as the hypotensive effect of L-arginine were abolished by the guanylate cycla se inhibitor Methylene blue (0.3 mu mol, i.t.). Nicotinic ganglionic b lockade by hexamethonium (10 mg/kg, i.v.) reduced the hypotensive effe cts of both L-arginine and SNP and prevented almost completely the pre sser effects of either L-NAME or SNP. The presser effect of L-NAME was abolished by 2-amino-5-phosphonovaleric acid (APV; 30 nmol, i.t.), a selective antagonist of glutamate receptors of the NMDA subtype. These results suggest that in the spinal cord of pentobarbital-anesthetized rats NO exerts both inhibitory and excitatory effects on the pregangl ionic sympathetic nerve activity related to the control of the BP. The synthesis of NO appears to be tonically activated through the stimula tion of spinal glutamate receptors of the NMDA subtype. (C) 1997 Elsev ier Science B.V.