ROLE OF OUABAIN-LIKE COMPOUND IN THE ROSTRAL VENTROLATERAL MEDULLA INRATS

To determine whether ouabain-like compound (OLC) exerts modulatory inf luences on the activity of vasomotor neurons in the rostral ventrolate ral medulla (RVLM), we examined the effects of microinjecting ouabain, digoxin-specific antibody Fab fragments, and mAb against ouabain on t he rat RVLM. Microinjection of ouabain into the unilateral RVLM of ane sthetized normotensive rats elicited dose-dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). T he presser and sympathoexcitatory effects of ouabain in the RVLM were reversed by microinjections of an M-2 muscarinic antagonist, gallamine , or digoxin-specific antibody Fab fragments. Furthermore, a prior mic roinjection in the RVLM of gallamine, digoxin-specific antibody Fab fr agments, or kainic acid or intravenous injection of hexamethonium all prevented the presser and sympathoexcitatory effects induced by a subs equent microinjection of ouabain. Microinjections of either digoxin-sp ecific antibody Fab fragments or gallamine per se significantly decrea sed baseline MAP and RSNA. Injection of digoxin-specific antibody Fab fragments attenuated the effects of a subsequent injection of gallamin e, Microinjection of mAb against ouabain, but not nonspecific IgG, als o significantly decreased baseline MAP and RSNA. These results suggest that OLC in the RVLM contributes to the tonic activity of vasomotor n eurons in anesthetized normotensive rats, and the action of OLC in the RVLM is at least partly mediated by M-2 muscarinic mechanisms.