Effects of neuropeptides on heart rate in dogs: comparison of VIP, PHI, NPY, CGRP, and NT.

This study was designed to evaluate the potential chronotropic actions of several cardiac neuropeptides in pentobarbital-anesthetized dogs. After bilateral vagotomy and stellectomy and muscarinic receptor blockade, I injected vasoactive intestinal polypeptide, peptide histidine isoleucine, neuropeptide Y, neurotensin, and calcitonin gene-related peptide into the intact sinus node artery. Neurotensin, calcitonin gene-related peptide, and neuropeptide Y exhibited no physiologically significant changes in heart rate. However, the structural homologues vasoactive intestinal polypeptide and peptide histidine isoleucine each augmented heart rate with maximal increases (approximately 120 beats/min) similar to those of norepinephrine. Vasoactive intestinal polypeptide and peptide histidine isoleucine were twice and 1/18, respectively, as potent as norepinephrine. The cardioacceleratory responses to vasoactive intestinal polypeptide and peptide histidine isoleucine were more slowly developing and longer lasting than those of norepinephrine. The responses to these two peptides were unchanged after beta-adrenergic blockade with propranolol in a dose sufficient to eliminate or greatly attenuate the norepinephrine tachycardia. These results indicate a potential role of endogenous vasoactive intestinal polypeptide and peptide histidine isoleucine in nonadrenergic, noncholinergic heart rate control in the dog.