Substance P Evokes Bradycardia via Cholinergic Neurons in Anesthetized Guinea Pigs

Urethane anesthetized guinea pigs exhibit a decrease in heart rate (HR) upon i.v. injection of substance P (SP). The purpose of this project was to determine if this effect is due to cholinergic stimulation by SP. Male Hartley guinea pigs (400-650g) were anesthetized with urethane (1.5 g/kg, i.p.) and bilaterally vagotomized. Blood pressure was recorded by cannulation of the left carotid artery. Heart rate (HR) was derived from the pressure signal. The trachea was cannulated to allow for artificial respiration. SP, saline and other drugs were injected (50 μl bolus) through a cannula in the left jugular vein. SP (32 nmol/kg) produced a brief bradycardia and prolonged hypotensive response under these conditions. After control responses to SP, animals were either given a muscarinic antagonist (atropine) or a cholinesterase inhibitor (physostigmine). The bradycardia evoked by the second injection of SP was attenuated by atropine (1 μmol/kg; n=5, P=0.041) and augmented by physostigmine (0.9 μmol/kg; n=5, P=0.050). These results suggest that the negative chronotropic response to SP is mediated by cholinergic neurons