GABAERGIC AND GLUTAMINERGIC MODULATION OF CENTRALLY EVOKED ARRHYTHMIAS IN RATS

A standard electrical stimulus applied to the posterior hypothalamus e voked cardiac arrhythmogenic responses in the spontaneously hypertensi ve rat. Isolated premature ventricular beats or doublets and nonsustai ned ventricular tachycardic salves were observed. This effect was asso ciated with a large rise in blood pressure (79+/3 mm Hg). The same sti mulus in normotensive Wistar-Kyoto rats produced no significant cardia c arrhythmias, and the rise in blood pressure was smaller (36+/-2 mm H g). We investigated the influence of baclofen, a GABA(B) receptor agon ist, and two N-methyl-D-spartate receptor antagonists on the arrhythmo genic response to hypothalamic stimulation. Intravenous baclofen (3 mg /kg) had no effect in the normotensive Wistar-Kyoto rats, but in the s pontaneously hypertensive rats it enhanced the adjusted mean value of the number of extrasystoles from 0.5+/-0.5 to 18+/-1 (P<.001). This va lue was also increased (from 3+/-1 to 17+/-1, P<.001) by an intraciste rnal injection of baclofen (1 mu g/kg). This facilitatory effect of ba clofen was prevented by treatment with atenolol (0.,5 mg/kg). Two glut amate receptor antagonists, ketamine (7.5 mg/kg IV) and kynurenic acid (200 mu g/kg intracerebroventricularly), prevented both the arrhythmo genic response to the hypothalamic stimulation and its facilitation by baclofen. The study confirms that hypothalamic stimulation facilitate s the development of arrhythmias through a sympathetic drive and that these arrhythmias are easier to induce in spontaneously hypertensive r ats than in normotensive Wistar-Kyoto rats. Both the central GABAergic and the glutamatergic systems are implicated in the development of th ese ventricular arrhythmias, since baclofen could disinhibit the gluta matergic central pathway. These results could account for the ability of the spontaneously hypertensive rats to develop ventricular arrhythm ias of central origin.