Centrally induced reduction in sympathetic tone — A postsynaptic α-adrenoceptor-stimulating action of imidazolines

Abstract

Naphazoline or oxymetazoline (both 30 μg/kg) were injected into the cisterna magna of anaesthetized cats and reduced blood pressure, heart rate and the electrical discharge rate of small fibre bundles of the preganglionic sympathetic splanchnic nerve. Cats were depleted of endogenous noradrenaline by pretreatment with reserpine (5 mg/kg, 18 h) and α-methyl-p-tyrosine) twice 300 mg/kg, 18 and 2 h). In these animals, intracisternal injection of 30 μg/kg oxymetazoline exerted a decrease of sympathetic discharges similar to that described for non-pretreated animals. In noradrenaline-depleted cats intracisternal injection of 1 μg/kg clonidine also decreased the sympathetic discharges. It is concluded that these imidazolines exert their sympathoinhibitory and cardiovascular effects by stimulation of postsynaptic α-adrenoceptors in the CNS. In the isolated rat vas deferens, oxymetazoline was a much weaker agonist (intrinsic activity (i.a.) < 0.1) than naphazoline and clonidine (i.a. 0.6 or 0.8 respectively). All three imidazolines exerted considerable competitive antagonism against noradrenaline, with oxymetazoline being the most potent antagonist (pA 2: 6.0; clonidine 5.0; naphazoline 5.5). The order of agonistic activities of the three imidazolines on the vas deferens is different from that on other peripheral adrenergic systems and indicates different α-adrenoceptors. The possibility of receptor differences in the CNS is discussed.