BACLOFEN PREVENTS THE INCREASE OF MYOCARDIAL OXYGEN-DEMAND INDEXES EVOKED BY THE HYPOTHALAMIC-STIMULATION IN RABBITS

The electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus in anaesthetized rabbits elicited important cardiovascul ar responses which were mainly characterized by increases in arterial pressure, dP/dt(max), and of the indexes of myocardial oxygen consumpt ion, rate-pressure product (from 34+/-2 to 40+/-2 mmHg.bpm.10(-3) and triple product (from 102+/-12 to 162+/-19 mmHg2.s-1.bpm.10(-6)). The h emodynamic alterations induced by PVN stimulation were similar to thos e observed during physical effort and stressful situations. Intracereb roventricular (0.1, 0.3 and 1 mug.kg-1) or intravenous administration (1, 3 and 10 mg.kg-1) of baclofen, a selective GABA(B) receptor agonis t, induced a dose-related decrease in the peak values of dP/dt(max) an d of the indexes of myocardial oxygen consumption (rate-pressure and t riple products) during the electrical PVN stimulation. After 1 mug.kg- 1 baclofen (i.cv.), the peak value of the triple product during PVN st imulation was 101+/-21 as compared to 149+/-15 before treatment. At th e 10 mg.kg-1 dose (i.v.), the triple product during stimulation only r eached 90+/-20 vs. 150+/-20 before treatment. These results suggested that a type B GABAergic transmission system is involved in the modulat ion of central control of the cardiac function. Drugs modulating this system could therefore be designed to blunt the myocardial oxygen dema nd increases.