THE NON-NMDA SUBTYPE OF EXCITATORY AMINO-ACID RECEPTOR PLAYS THE MAJOR ROLE IN CONTROL OF CARDIOVASCULAR FUNCTION BY THE SUBRETROFACIAL NUCLEUS IN CATS

Recent studies have reported that microinjection of kynurenic acid (KY N 12.5 nmol), the nonselective Excitatory Amino acid (EAA) antagonist, into the rostral ventrolateral medulla of the cat decreases arterial blood pressure (BP) and inferior cardiac sympathetic nerve discharge. The purpose of our study was to confirm this finding and determine the subtypes of EAA receptor(s) responsible for mediating this effect. Th is was done by microinjecting various EAA antagonists bilaterally into the SRFN of chloralose-anesthetized animals while monitoring BP and H R. KYN (12.5 nmol; N = 5) produced a decrease in mean BP (31 +/- 9 mmH g, P < .05) with no significant change in HR. To determine the subtype of EAA receptor responsible for eliciting tonic sympathetic outflow f rom the SRFN, specific antagonists of N-methyl-D-aspartate (NMDA) and non-NMDA EAA receptors were tested. The NMDA receptor antagonist 3-(RS )-Carboxypiperazin-4-yl)-proyl-1 -phosphonic acid (CPP- 2.25 nmol; N = 3) microinjected into the SRFN produced a small but significant decre ase in BP (-13 +/- 1 mmHg; P < .05). This effect of CPP was significan tly less than that seen with KYN. Two antagonists of the non-NMDA subt ype of EAA receptor, 6-cyano-7-nitroquinoxaline-2,3-dione (0.05 nmol; N = 4) and gamma-D-glutamylaminomethyl sulphonic acid (2.5 nmol; N = 4 ), were microinjected into the SRFN. Both of these drugs produced decr eases in BP (-29 +/- 4 and -23 +/- 3 mmHg, respectively; P < 0.05) sim ilar to that observed with KYN. No significant changes in HR were note d with CPP, 6 cyano-7-nitroquinoxaline-2,3-dione or gamma-D-glutamylam ino-methylsulfonate. These data indicate that a non-NMDA EAA receptor plays the major role in control of cardiovascular function by the SRFN .