Blockade of central nervous system GABAergic tone causes sympathetic-mediated increases in coronary vascular resistance in cats

Circulation Research
S A SegalR Gillis

Abstract

Picrotoxin, an antagonist of gamma-aminobutyric acid, produces an increase in coronary vascular resistance, S-T segment elevation, and ventricular arrhythmias after an intravenous injection of 2 mg/kg in chloralose-anesthetized cats. To determine whether these responses were due to blockade of central nervous system GABAergic mechanisms leading to an increase in sympathetic outflow to the coronary vasculature, several types of experiments were performed. First, picrotoxin was injected directly into the brain in a dose of 600 micrograms while coronary blood flow and S-T segment changes were monitored. Central nervous system administration of this agent resulted in a significant increase in coronary vascular resistance, S-T segment elevation, and arrhythmias. Second, animals were pretreated with the gamma-aminobutyric acid receptor agonist drug, muscimol, prior to central administration of picrotoxin. Pretreatment prevented the usual increase in coronary vascular resistance, S-T segment elevation, and arrhythmias. Third, animals were subjected to acute bilateral cardiac sympathetic denervation prior to picrotoxin administration. Denervation attenuated the picrotoxin-induced increase in coronary vascular resistance (mean = 11.6 +/...Continue Reading

References

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