Effects of ifenprodil and baclofen on exercise-induced increase of myocardial oxygen demand in normotensive rats

Central glutamatergic relays are known to be present in the central sympathetic pathways. Ifenprodil (an N-methyl-D-aspartate antagonist) and baclofen (a gamma-aminobutyric acid, agonist) are both modulators of these synapses; we previously reported their ability to reduce the cardiovascular responses induced by a central hypothalamic stimulation in rabbits. In this work, we investigated the actions of chronic treatments with these two drugs on the increase of myocardial oxygen demand induced by exercise in normotensive rats. Moreover, their effects on the baroreceptor heart rate reflex were observed. Male normotensive WKY rats were treated with placebo (two groups), baclofen, or ifenprodil for 14 days. They were then submitted to a progressively increased exercise test on a treadmill. In another three groups of animals, the same treatment was applied but, at the end, a baroreflex study was performed by the injection of phenylephrine (vagal component of the reflex) and of sodium nitroprusside (sympathetic component). Ifenprodil and baclofen reduced by nearly 50% the level of the increase of the rate x pressure product during exercise as compared with control rats. This effect appeared to be mainly due to a reduction of the hypertensive response. In the same conditions, neither baclofen nor ifenprodil significantly altered the baroreceptor heart rate reflex. The fact that these two drugs are capable of reducing the myocardial oxygen demand encourages us to test them in a model of myocardial ischemia associated with sympathetic hyperactivity.