Role of calcitonin gene-related peptide as cardiotonic neurotransmitter in guinea pig left atria.

A potential neurotransmitter role of calcitonin gene-related peptide (CGRP) in nonadrenergic noncholinergic (NANC) nerves was examined in the left atrium of guinea pigs. In the presence of atenolol (beta-adrenoceptor antagonist), prazosin (alpha adrenoceptor antagonist) and atropine (muscarinic antagonist), transmural nerve stimulation (TNS) elicited a positive inotropic response which was slow in both onset and decay. Inasmuch as this TNS-induced positive inotropic response was abolished by tetrodotoxin, it can be considered that the response was mediated by intracardiac NANC nerves. Numerous CGRP-like immunoreactive nerves were detected in the left atrium. Exogenously applied CGRP produced a positive inotropic response in a dose-dependent manner. Neither substance P nor vasoactive intestinal polypeptide exerted a positive inotropic effect. CGRP-like immunoreactive nerves and the TNS-induced NANC response was not affected by surgical sympathectomy of the heart or reserpine pretreatment but were specifically abolished by the pretreatment of animals with capsaicin. These results suggest that CGRP is the potential neurotransmitter of NANC nerves in the left atrium of guinea pigs.