The Prelimbic Cortex Muscarinic M3 Receptor-Nitric Oxide-Guanylyl Cyclase Pathway Modulates Cardiovascular Responses in Rats

The prelimbic cortex (PL), a limbic structure, sends projections to areas involved in the control of cardiovascular responses. Stimulation of the PL with acetylcholine (ACh) evokes depressor and tachycardiac responses mediated by local PL muscarinic receptors. Early studies demonstrated that stimulation of muscarinic receptors induced nitric oxide (NO) synthesis and cyclic guanosine cyclic monophosphate (cGMP) formation. Hence, this study investigates which PL muscarinic receptor subtype is involved in the cardiovascular response induced by ACh and tests the hypothesis that cardiovascular responses caused by muscarinic receptor stimulation in the PL are mediated by local NO and cGMP formation. PL pretreatment with J104129 (an M-3 receptor antagonist) blocked the depressor and tachycardiac response evoked by injection of ACh into the PL. Pretreatment with either pirenzepine (an M-1 receptor antagonist) or AF-DX 116 (an M-2 and M-4 receptor antagonist) did not affect cardiovascular responses evoked by ACh. Moreover, similarly to the antagonism of PL M-3 receptors, pretreatment with Nxpropyl- L-arginine (an inhibitor of neuronal NO synthase), carboxy-PTIO(S)-3-carboxy-4-hydroxyphenylglicine (an NO scavenger), or H-1-[1,2,4] oxadiazolol-[4,3-a] quinoxalin-1- one (a guanylate cyclase inhibitor) blocked both the depressor and the tachycardiac response evoked by ACh. The current results demonstrate that cardiovascular responses evoked by microinjection of ACh into the PL are mediated by local activation of the M-3 receptor-NO- guanylate cyclase pathway. (C) 2015 Wiley Periodicals, Inc.