Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis

The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist muscimol (0.01-1 μg) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 ± 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of -52.7 ± 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatment with atropine (2 mg/kg, ip, or 15 mg/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 ± 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was -12.1 ± 1.6 mm Hg from 109.3 ± 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats. Following 1 μg muscimol, icv, plasma noradrenaline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 ± 24.2 to 22.8 ± 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 μg muscimol, icv. Basal adrenal nerve activity was higher in stroke prone spontaneously hypertensive than in Wistar-Kyoto rats (14.8 ± 3.7 vs. 10.6 ± 1.7 μV, P<0.02); it was reduced by 44% in stroke prone-spontaneously hypertensive rats and only by 24% in Wistar-Kyoto rats after central muscimol administration. In contrast to muscimol, the central antihypertensive action of the α₂-adrenoceptor agonist clonidine in conscious stroke prone spontaneously hypertensive rats was accompanied by similar reductions of splanchnic nerve activity (28%) and adrenal activity (25%). Our results demonstrate for the first time an increased efferent adrenal nerve activity in conscious stroke prone spontaneously hypertensive rats and a selective inhibition of the sympathoadrenal pathway by central GABA-ergic stimulation. The antihypertensive action of central GABA receptor stimulation in stroke prone spontaneously hypertensive rats is not mediated by an increase in vagal tone or a generalized reduction in sympathetic tone, but is associated with the selective suppression of sympathoadrenal activity.