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    NO-cGMP pathway at ventrolateral medullary cardiac inhibitory sites enhances the baroreceptor reflex bradycardia in the rat.

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    Authors
    Fletcher, Janine
    Moody, William E.
    Chowdhary, Saqib
    Coote, John H.
    Issue Date
    2006
    
    Metadata
    Show full item record
    Abstract
    The neuronal isoform of the enzyme nitric oxide synthase (nNOS) has been identified in the caudal ventrolateral medulla of the rat close to the location of cardiac vagal motoneurones. Therefore in this study we tested identified ventral medulla cardioinhibitory sites for the involvement of nitric oxide (NO) in the baroreceptor-heart rate reflex pathway. In rats anaesthetised with a mixture of urethane (650 mg kg(-1)) and chloralose (50 mg kg(-1)) i.v., blood pressure and heart rate were monitored continuously and using stereotaxic coordinates the ventrolateral caudal brainstem within and around the nucleus ambiguus was systematically explored for sites producing a bradycardia of >50 bpm, without a change in blood pressure, using D,L homocysteic acid (DLH, 0.2 M) microinjections (50 nl) from a glass micropipette. Identified sites were marked with pontamine sky blue. Microinjection of the NO donor sodium nitroprusside (SNP, 1 mM, 50 nl) at a cardioinhibitory site also produced a significant bradycardia (68+/-14 bpm) while the NOS inhibitor N(G)-nitro-l-arginine (l-NNA) (3 mM, 50 nl) caused a small significant increase in heart rate (5+/-1 bpm). Baroreceptor reflex gain measured by the response in heart rate to a change in blood pressure induced by phenylephrine i.v. was significantly increased (610+/-171%, p<0.05) during the steady state of the response to SNP, whereas it was significantly reduced (73+/-5%, p<0.01) by l-NNA injection at a medullary cardioinhibitory site. An inhibitor of soluble guanylyl cyclase, (1)H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ, 1 mM, 50 nl) also significantly reduced the baroreceptor reflex gain (63+/-8%, p<0.05). The results suggest that a NOS-cGMP signalling system in the baroreceptor reflex pathway distal to the NTS and closer to cardiac vagal motoneurones in the caudal ventral medulla contributes to enhancement of cardiac vagal tone.
    Citation
    Brain Research, 1123(1): 125-134
    Publisher
    Elsevier BV
    URI
    http://hdl.handle.net/2436/15837
    DOI
    10.1016/j.brainres.2006.09.024
    PubMed ID
    17064669
    Additional Links
    http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYR-4M645CG-4&_user=1644469&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000054077&_version=1&_urlVersion=0&_userid=1644469&md5=13fa4b1ae1c6a59a14b5b941c982c7b5
    Type
    Journal article
    Language
    en
    Description
    Metadata only
    ISSN
    0006-8993
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.brainres.2006.09.024
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