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The prelimbic cortex muscarinic M 3 receptor–nitric oxide–guanylyl cyclase pathway modulates cardiovascular responses in rats
Author(s) -
Fassini Aline,
Antero Leandro S.,
Corrêa Fernando M.A.,
Joca Sâmia R.,
Resstel Leonardo B.M.
Publication year - 2015
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23537
Subject(s) - muscarinic acetylcholine receptor , endocrinology , medicine , pirenzepine , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m3 , acetylcholine , chemistry , muscarinic acetylcholine receptor m4 , stimulation , receptor , receptor antagonist , soluble guanylyl cyclase , antagonist , nitric oxide , biology , guanylate cyclase
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 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 M 3 receptor–NO–guanylate cyclase pathway. © 2015 Wiley Periodicals, Inc.