ALPHA-ADRENOCEPTOR MODULATION OF THE EFFERENT FUNCTION OF CAPSAICIN-SENSITIVE SENSORY NEURONS IN GUINEA-PIG ISOLATED ATRIA

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-mu-M and of the beta-adrenoceptor blocker CGP 20712A 1-mu-M, 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-mu-M. 2 Noradrenaline concentration-dependently (0.01 - 10-mu-M) reduced the increase in cardiac contractility induced by transmural nerve stimulation. The inhibitory effect of noradrenaline was antagonized by yohimbine (0.5 - 1-mu-M), in a dose-dependent manner. Prazosin (0.5 - 1-mu-M) 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-mu-M phenoxybenzamine. 4 The selective alpha(2) agonists BHT 920 and clonidine reduced, in the same concentration-range (0.01 - 1-mu-M), the cardiac response to transmural nerve stimulation in a yohimbine-sensitive fashion. 5 Phenylephrine (0.1 - 100-mu-M) and methoxamine (1 - 300-mu-M) also induced an inhibitory effect on transmural nerve stimulation. The effect of phenylephrine was antagonized by yohimbine (1-mu-M) more efficiently than by prazosin (0.5-mu-M). 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.