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(Hypertension. 1996;27:148-154.)
© 1996 American Heart Association, Inc.

Articles

GABAergic and Glutaminergic Modulation of Centrally Evoked Arrhythmias in Rats

Anne Crambes; Laurent Monassier; Denis Chapleau; Jean-Christophe Roegel; Josiane Feldman; Pascal Bousquet

From the Laboratoire de Pharmacologie Cardiovasculaire et Rénale, Centre National de Recherche Scientifique Unité de Recherche Associée 589, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France, and the Département de Chirurgie, Faculté de Médecine, Université de Montréal, Hôpital du Sacré-Coeur de Montréal, Québec, Canada (D.C.).

Correspondence to Anne Crambes, Hôpital du Sacré-Coeur de Montréal, 5400 Blvd Gouin Ouest, Montréal, Québec, Canada H4J 1C5.

Abstract A standard electrical stimulus applied to the posterior hypothalamus evoked cardiac arrhythmogenic responses in the spontaneously hypertensive rat. Isolated premature ventricular beats or doublets and nonsustained ventricular tachycardic salvos were observed. This effect was associated with a large rise in blood pressure (79±3 mm Hg). The same stimulus in normotensive Wistar-Kyoto rats produced no significant cardiac arrhythmias, and the rise in blood pressure was smaller (36±2 mm Hg). We investigated the influence of baclofen, a GABA_B receptor agonist, and two N-methyl-D-aspartate receptor antagonists on the arrhythmogenic response to hypothalamic stimulation. Intravenous baclofen (3 mg/kg) had no effect in the normotensive Wistar-Kyoto rats, but in the spontaneously hypertensive rats it enhanced the adjusted mean value of the number of extrasystoles from 0.5±0.5 to 18±1 (P<.001). This value was also increased (from 3±1 to 17±1, P<.001) by an intracisternal injection of baclofen (1 µg/kg). This facilitatory effect of baclofen was prevented by treatment with atenolol (0.5 mg/kg). Two glutamate receptor antagonists, ketamine (7.5 mg/kg IV) and kynurenic acid (200 µg/kg intracerebroventricularly), prevented both the arrhythmogenic response to the hypothalamic stimulation and its facilitation by baclofen. The study confirms that hypothalamic stimulation facilitates the development of arrhythmias through a sympathetic drive and that these arrhythmias are easier to induce in spontaneously hypertensive rats than in normotensive Wistar-Kyoto rats. Both the central GABAergic and the glutamatergic systems are implicated in the development of these ventricular arrhythmias, since baclofen could disinhibit the glutamatergic central pathway. These results could account for the ability of the spontaneously hypertensive rats to develop ventricular arrhythmias of central origin.

Key Words: rats, inbred SHR • rats, inbred WKY • hypothalamus • arrhythmia • receptors, glutamate • receptors, GABA