The non-NMDA subtype of excitatory amino acid receptor plays the major role in control of cardiovascular function by the subretrofacial nucleus in cats

TP Abrahams, PJ Hornby, K Chen, AM Dasilva and RA Gillis

Department of Pharmacology, Georgetown University, School of Medicine, Washington, D.C.

Recent studies have reported that microinjection of kynurenic acid (KYN 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. This was done by microinjecting various EAA antagonists bilaterally into the SRFN of chloralose-anesthetized animals while monitoring BP and HR. KYN (12.5 nmol; N = 5) produced a decrease in mean BP (31 +/- 9 mmHg, P < .05) with no significant change in HR. To determine the subtype of EAA receptor responsible for eliciting tonic sympathetic outflow from 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 decrease in BP (-13 +/- 1 mmHg; P < .05). This effect of CPP was significantly less than that seen with KYN. Two antagonists of the non-NMDA subtype 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 decreases in BP (-29 +/- 4 and -23 +/- 3 mmHg, respectively; P < 0.05) similar to that observed with KYN. No significant changes in HR were noted with CPP, 6 cyano-7-nitroquinoxaline-2,3-dione or gamma-G- glutamylamino-methylsulfonate. These data indicate that a non-NMDA EAA receptor plays the major role in control of cardiovascular function by the SRFN.

Volume 270, Issue 1, pp. 424-432, 07/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics