Pirenzepine-sensitive component of forelimb vascular resistance and heart rate in cats

In vagotomized, midcollicular decerebrate, non-anesthetized cats, in which the preganglionic input to the stellate ganglion was intact and the right forelimb was autoperfused at constant flow, the muscarinic receptor antagonist pirenzepine (PZP, 50 micrograms/kg i.v.), which does not cross the blood-brain barrier, produced a decrease in forelimb perfusion pressure (FLPP), heart rate (HR) and systemic arterial pressure (SAP). Administration of the nicotinic receptor antagonist hexamethonium (30 mg/kg i.v.) after PZP produced a further, larger drop in FLPP, HR and SAP. The dose of PZP used blocked the increase in FLPP and HR evoked by the muscarinic receptor agonist McN-A-343, but not the increase evoked by the nicotinic receptor agonist DMPP, when these drugs were injected into the arterial supply of the ganglion. Following administration of phentolamine and propranolol (2 mg/kg i.v. of each) which caused bradycardia and forelimb vasodilation, PZP had no effect on FLPP and HR. This finding suggests that PZP decreases sympathetic tone in resistance vessels and in the heart. Pirenzepine did not depress the forelimb vasoconstriction and the cardioacceleration evoked by electrical stimulation of the postganglionic vertebral and inferior cardiac nerves, respectively, suggesting that PZP does not act at the neuro-effector junctions. On the other hand, PZP blocked the forelimb vasoconstriction and the cardioacceleration produced by stimulating the preganglionic input of the stellate ganglion in presence of hexamethonium (30 mg/kg i.v.), indicating the stellate ganglion as the likely site of action of the drug. These findings suggest that the ganglion cell firing that underlies the sympathetic tone of cardiovascular effector cells is generated, in part, by a muscarinic, PZP-sensitive, synaptic mechanism.