INHIBITION OF THE CENTRALLY INDUCED INCREASES IN MYOCARDIAL OXYGEN-DEMAND IN RABBITS BY CHRONIC TREATMENT WITH BACLOFEN, A SELECTIVE GABA(B) AGONIST

1 A previous study from our group demonstrated that neurones of the pa raventricular nucleus of the hypothalamus (PVN) are selectively involv ed in the central control of the cardiac function. Moreover, in that s tudy, it was shown that baclofen, a selective GABAB receptor agonist, is capable of modulating the increases in myocardial contractility and oxygen demand evoked by electrical or pharmacological stimulation of the PVN. Nevertheless, the acute administration of this compound was f requently accompanied by a cardiodepressant effect. 2 In the present s tudy, the effects of a long term treatment (14 days) with baclofen (3 or 10 mg kg(-1), i.p.) have been examined on the excitatory haemodynam ic responses evoked by central pharmacological stimulation in anaesthe tized rabbits. 3 The i.c.v. injection of L-glutamate (3 mg kg(-1)) ind uced marked increases in dP/dt(max) (32%), mean arterial pressure (39% ) and on two indices of myocardial oxygen consumption: the rate-pressu re product (34%) and the triple product (78%). 4 Baclofen blunted the positive inotropic response and the increases in myocardial oxygen con sumption induced by L-glutamate in a dose-related manner. The higher d ose of baclofen (10 mg kg(-1), i.p.), reduced by more than 50% these e xcitatory effects of L-glutamate without eliciting any significant neg ative effect on basal haemodynamics. The same doses of baclofen were n ot able to blunt the hypertensive response induced by central stimulat ion. 5 These results confirm and extend our previous findings suggesti ng that it is possible to discriminate the central control of vasomoto r tone from that of cardiac function and also that baclofen can modula te the latter. It is concluded that when given chronically, baclofen m odulates the increases in myocardial oxygen demand induced by activati on of the central nervous system in doses which do not depress the res ting cardiac function.