PREVENTION BY NMDA RECEPTOR ANTAGONISTS OF THE CENTRALLY-EVOKED INCREASES OF CARDIAC INOTROPIC RESPONSES IN RABBITS

1 The purpose of this study was to investigate further the role of the excitatory amino acid (EAA) system of neurotransmission, particularly of the NMDA receptor, in the central regulation of cardiac function. 2 Electrical stimulation of the paraventricular nucleus of the hypotha lamus (PVN) in pentobarbitone anaesthetized rabbits induced a cardiova scular response mainly characterized by a positive inotropic effect, h ypertension and a marked increase in the myocardial oxygen demand inde x. 3 The intracerebroventricular (i.c.v.) or intravenous (i.v.) inject ion of different EAA antagonists acting on different sites of the NMDA receptor/channel complex dose-dependently blunted the excitatory card iovascular effects of PVN stimulation. 4 5,7 Dichlorokynurenic acid wa s used as a specific glycine site antagonist and 2-amino-5-phosphonova leric acid was used to block the agonist recognition site; ketamine wa s used as a channel blocker site antagonist and ifenprodil as a blocke r of the polyamine binding site. 5 5,7 Dichlorokynurenic acid (125 and 250 mug kg-1, i.c.v.) virtually abolished the cardiovascular response s, inducing only haemodynamic depression at the highest dose used. 2-A mino-5-phosphonovaleric acid (0.1 to 1.0 mg kg-1, i.c.v.) elicited a r eduction of the peak values observed during PVN stimulation which was accompanied by a decrease of the basal cardiovascular parameters. Keta mine (2.5 and 10 mg kg-1) and ifenprodil (1 mg kg-1), injected intrave nously, blocked the haemodynamic response induced by PVN stimulation w ithout marked reduction of the basal haemodynamics. 6 It is concluded that glutamate neurotransmission is not only involved in vasomotor ton e control but also in the central control of cardiac function and can therefore modulate the myocardial oxygen demand.