Specific subtypes of nicotinic cholinergic receptors involved in sympathetic and parasympathetic cardiovascular responses

Abstract

Various subtypes of nicotinic cholinergic receptors are expressed in autonomic ganglia. The distinct functional roles of these receptors in autonomic ganglionic transmission to different target organs remain to be elucidated. In this study, we tested the sympathetic and parasympathetic cardiovascular responses to nicotinic agonist and antagonists in urethane-anesthetized mice. Intravenous injection with a nicotinic agonist, 1,1-dimethyl-4-phenylpiperazinium iodide, induced a brief but pronounced decrease in heart rate, followed by significant increases in heart rate and arterial blood pressure. The bradycardic response was blocked by atropine whereas the pressor response was blocked by prazosine, confirming those responses were parasympathetic and sympathetic activities, respectively. The sympathetic response was blocked by methyllycaconitine citrate, a selective α7 nicotinic cholinergic receptor (nAchR) antagonist. The parasympathetic response was blocked by a selective α4β2 nAchR antagonist, dihydro-β-erythroidine hydrobromide. Moreover, injection with a selective α4β2 nAchR agonist, RJR2403 oxalate, induced a pronounced parasympathetic response with a smaller sympathetic response. Collectively, these data show that activations of α4β2 nAchRs elicits a parasympathetic cardiovascular response and activation of α7 nAchRs elicits a sympathetic cardiovascular response. These data suggest that specific subtypes of nicotinic receptors at the level of the ganglia may play distinct roles in mediating sympathetic or parasympathetic activation.