α.‐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-', i.p.), in the presence of atropine 1 JAM and of the 13-adrenoceptor blocker CGP 20712A 1 JAM, 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 JM.2 Noradrenaline concentration-dependently (0.01-10 JAM) reduced the increase in cardiac contractility induced by transmural nerve stimulation. The inhibitory effect of noradrenaline was antagonized by yohimbine (0.5-1 JM), in a dose-dependent manner. Prazosin (0.5-1 JAM) 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 JAM phenoxybenzamine. 4 The selective X2 agonists BHT 920 and clonidine reduced, in the same concentration-range (0.01-1 JAM), the cardiac response to transmural nerve stimulation in a yohimbine-sensitive fashion.5 Phenylephrine (0.1-100 JAM) and methoxamine (1-300 JAM) also induced an inhibitory effect on transmural nerve stimulation. The effect of phenylephrine was antagonized by yohimbine (1 JM) more efficiently than by prazosin (0.5 JM). 6 These results are in keeping with the presence of inhibitory prejunctional a2-adrenoceptors on cardiac sensory nerve endings which modulate the efferent function of capsaicin-sensitive neurones.

Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block

“…The prolongation of TTX block appeared to be receptor-mediated (as opposed to a nonspecific effect) as evidenced by its inhibition by concentrations of adrenergic antagonists that are comparable to those reported for other physiologic processes (e.g., modulation of atrial neuronal function, 18 inhibition of cerebral cortical histamine release, 19 reduction of clonidine's effect on inward current in motor neu-rons, 20 and clonidine's effect on spinal segmental reflexes. 21 Beta-adrenergic receptor stimulation did not prolong TTX block, and in fact, reduced its duration by 40%.…”

Calcitonin Gene-Related Peptide In Vivo Positive Inotropy Is Attributable to Regional Sympatho-Stimulation and Is Blunted in Congestive Heart Failure

“…The fibers involved with CGRP sympatho-stimulation are likely those innervating the ventricles directly, given the localized myocardial norepinephrine response. Norepinephrine can also act on sensory cardiac nerve endings and resistance vessels to attenuate CGRP release 33,34 ; whether such a feedback loop played a role in the current study is unclear. A similar circuit has been proposed for CGRP and histamine release from local mast cells to activate H 3 receptors on C-fiber endings, leading eventually to CGRP release inhibition.…”