Muscarinic inhibition of endogenous myocardial catecholamine liberation in the dog

Abstract

The release of endogenous catecholamine (CA) into the coronary sinus of the anesthetized dog was investigated under basal sympathetic tone and during sympathetic and vagal electrical stimulation. Under basal conditions, right distal cervical vagal stimulation (1, 2, 4, 8, 16 Hz) did not significantly alter the output of CA into the conorary sinus although important increases in aortic CA levels were observed. Stimulation of the right cardioaccelerator nerves (10 Hz) caused a marked and reproducible increase in coronary sinus CA levels but this effect could be progressively attenuated by superposing vagal stimulation at increasing frequencies. A maximal inhibition (66%) of CA liberation was observed at a vagal stimulation frequency of 16 Hz. Atropine (2 μg/kg) blocked selectively the effect of low frequency vagal stimulation. Methacholine (3 μg/kg per minute) infusion mimicked vagal inhibition on CA liberation. It is suggested that a functional vagal inhibition of sympathetic CA liberation could be mediated through activation of presynaptic muscarinic receptors located on the adrenergic fibers within the left ventricle of the dog; moreover, the excellent correlation observed between the decrease in CA liberation and the first derivative of left ventricular pressure (dp/dt) suggests that this inhibition is of physiological significance. Such mechanisms could be implicated in the local fine adjustments of neurotransmitter liberation and in the functional peripheral integration of both components of the autonomic nervous system.