title: The prelimbic cortex muscarinic M₃ receptor-nitric oxide-guanylyl cyclase pathway modulates cardiovascular responses in rats.
abstract: 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 M3 receptor antagonist) blocked the depressor and tachycardiac response evoked by injection of ACh into the PL. Pretreatment with either pirenzepine (an M1 receptor antagonist) or AF-DX 116 (an M2 and M4 receptor antagonist) did not affect cardiovascular responses evoked by ACh. Moreover, similarly to the antagonism of PL M3 receptors, pretreatment with N(ω)-propyl-L-arginine (an inhibitor of neuronal NO synthase), carboxy-PTIO(S)-3-carboxy-4-hydroxyphenylglicine (an NO scavenger), or 1H-[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 M3 receptor-NO-guanylate cyclase pathway.
authors.affiliation: Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Fassini
authors.forename: Leandro S
authors.initials: LS
authors.lastname: Antero
authors.forename: Fernando M A
authors.initials: FM
authors.lastname: Corrêa
authors.forename: Sâmia R
authors.initials: SR
authors.lastname: Joca
authors.forename: Leonardo B M
authors.initials: LB
authors.lastname: Resstel
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002540:Cerebral Cortex / Q000378:metabolism*; D018678:Cholinergic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D018678:Cholinergic Agents; D004791:Enzyme Inhibitors; D043587:Receptor, Muscarinic M3; D009569:Nitric Oxide; D006162:Guanylate Cyclase
keywords: cardiovascular; muscarinic receptors; nitric oxide; prelimbic cortex