Blockade of GABA receptors in periventricular forebrain of anesthetized cats: Effects on heart rate, arterial pressure, and hindlimb vascular resistance

Abstract

Pharmacologic antagonism of GABAergic inhibition in the periventricular forebrain of anesthetized cats caused dose related (1) sympathetically mediated increases in heart rate and arterial pressure in vagotomized cats, and (2) suppression of reflex vagal activation in vagus-intact preparations where sympathetic effects are prevented by cervical spinal cord transection. In the present study performed in cats with intact autonomic pathways, similar administration of the GABA antagonist bicuculline methiodide (BMI) produced dose-related increases in arterial pressure, heart rate, and, when perfusion pressure in the autoperfused hindlimb was measured, vascular resistance. Furthermore, the relationship between heart rate and hindlimb vascular resistance changes suggested that the effects on heart rate reflected the combined sympathetic and vagal baroreflex effects of BMI. Intraventricular administration of muscimol, a potent GABA agonist, elicited abrupt and parallel reversal of BMI-induced effects on systemic arterial pressure and vascular resistance while attempts to acutely denervate the hindlimb at the height of the BMI response by cutting the femoral and sciatic nerves sharply reversed the increase in hindlimb vascular resistance in most experiments. The results suggest that the cardiovascular changes observed represent an integrated pattern consisting of excitation of sympathetic nerves innervating the heart and vasculature along with suppression of reflex evoked vagal excitability.