Alpha-adrenoceptor modulation of the efferent function of capsaicin-sensitive sensory neurones in guinea-pig isolated atria.

Abstract

1. Transmural nerve stimulation of guinea-pig atria, obtained from animals pretreated with reserpine (5 mg kg-1, i.p.), in the presence of atropine 1 microM and of the beta-adrenoceptor blocker CGP 20712A 1 microM, induced a positive inotropic effect which was reduced by the calcitonin gene-related peptide (CGRP) antagonist hCGRP-(8-37) and abolished by pretreatment with capsaicin 1 microM. 2. Noradrenaline concentration-dependently (0.01-10 microM) reduced the increase in cardiac contractility induced by transmural nerve stimulation. The inhibitory effect of noradrenaline was antagonized by yohimbine (0.5-1 microM), in a dose-dependent manner. Prazosin (0.5-1 microM) antagonized the effect of noradrenaline and this effect was independent of concentration. 3. In the presence of yohimbine, the lower part of the inhibitory-response curve for noradrenaline was slightly but significantly shifted by prazosin. A similar degree of antagonism was observed in the presence of 1 microM phenoxybenzamine. 4. The selective alpha 2 agonists BHT 920 and clonidine reduced, in the same concentration-range (0.01-1 microM), the cardiac response to transmural nerve stimulation in a yohimbine-sensitive fashion. 5. Phenylephrine (0.1-100 microM) and methoxamine (1-300 microM) also induced an inhibitory effect on transmural nerve stimulation. The effect of phenylephrine was antagonized by yohimbine (1 microM) more efficiently than by prazosin (0.5 microM). 6. These results are in keeping with the presence of inhibitory prejunctional alpha 2-adrenoceptors on cardiac sensory nerve endings which modulate the efferent function of capsaicin-sensitive neurones.