Role of nitric oxide on pressor mechanisms within the dorsomedial and rostral ventrolateral medulla in anaesthetized cats

1. The role of nitric oxide (NO) in central cardiovascular regulation and t he correlation between NO and glutamate-induced mechanisms is not clear. Mi croinjection of glutamate (3 nmol/ 30 nL) into dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM) increased arterial blood pressure (BP ) and sympathetic vertebral nerve activity (VNA), Thus, in the present stud y, we examined the modulation by NO of glutamate-induced presser responses in the DM and RVLM of cats. 2, Histochemical methods using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) as a marker to stain neurons containing NO synthase (NO S), showed positive findings of NOS in both the DM and RVLM, 3, Microinjection of N-G-nitro-L-arginine methyl ester (L-NAME), a NOS inhi bitor, into the DM or RVLM did not alter resting EP and VNA, but it did cau se a dose-dependent attenuation of glutamate-induced presser responses. Int erestingly, the increase in NO levels that resulted from pretreatment with L-arginine (L-Arg) or sodium nitroprusside (SNP) did not alter resting BP a nd VNA, but still inhibited glutamate-induced presser responses in the DM a nd RVLM in a dose dependent manner. 4, We also examined whether NO modulated the presser responses induced by a ctivation of different excitatory amino acid receptors, N-Methyl-D-aspartat e (NMDA) and alpha -amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (A MPA) were used. Consistent with the results from the initial glutamate stud ies, we observed that not only L-NAME, but also L-Arg and SNP attenuated pr esser responses induced by NMDA and AMPA, No difference was found between t he effects of NO on NMDA- and AMPA-induced presser responses. 5. To investigate the possibility of a loss of agonist selectivity, the eff ects of D-2-amino-5-phosphonovalerate (D-AP5) and 6-cyano-7-nitroquinoxalin e-2,3-dione (CNQX) on AMPA and NMDA responses in the DM were examined. The results showed that CNQX did not alter NMDA-induced presser responses, whil e D-AP5 failed to alter AR;IPA-induced responses. 6. Our results suggest that activation of the glutamate-induced presser mec hanism is regulated by changes in NO levels in the DM and RVLM. This implie s that NO may play a permissive role to allow operation of the glutamate-ac tivation mechanism.