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Am J Physiol Heart Circ Physiol 293: H3465-H3470, 2007. First published September 28, 2007; doi:10.1152/ajpheart.00528.2007
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Effect of systemic B-type natriuretic peptide on cardiac vagal motoneuron activity

E. Toader,1 R. M. McAllen,2 A. Cividjian,1 R. L. Woods,2 and L. Quintin1

1Department of Physiology, Centre National de la Recherche Scientifique Unité Mixte de Recherche, University of Lyon, Lyon, France; and 2Howard Florey Institute, University of Melbourne, Victoria 3010, Australia

Submitted 3 May 2007 ; accepted in final form 22 September 2007

Intravenous B-type natriuretic peptide (BNP) enhances the bradycardia of reflexes from the heart, including the von Bezold-Jarisch reflex, but its site of action is unknown. The peptide is unlikely to penetrate the blood-brain barrier but could act on afferent or efferent reflex pathways. To investigate the latter, two types of experiment were performed on urethane-anesthetized (1.4 g/kg iv) rats. First, the activity was recorded extracellularly from single cardiac vagal motoneurons (CVMs) in the nucleus ambiguus. CVMs were identified by antidromic activation from the cardiac vagal branch and by their barosensitivity. Phenyl biguanide (PBG), injected via the right atrium in bolus doses of 1–5 µg to evoke the von Bezold-Jarisch reflex, caused a dose-related increase in CVM activity and bradycardia. BNP infusion (25 pmol·kg–1·min–1 iv) significantly enhanced both the CVM response to PBG (n = 5 rats) and the reflex bradycardia, but the log-linear relation between those two responses over a range of PBG doses was unchanged by BNP. The reflex bradycardia was not enhanced in five matched time-control rats receiving only vehicle infusions. In five other rats the cervical vagi were cut and the peripheral right vagus was stimulated supramaximally at frequencies of 1–20 Hz. The bradycardic responses to these stimuli were unchanged before, during, and after BNP infusion. We conclude that systemic BNP in a moderate dose enhances the von Bezold-Jarisch reflex activation of CVM, in parallel with the enhanced reflex bradycardia. That enhancement is due entirely to an action before the vagal efferent arm of the reflex pathway.

cardiopulmonary; von Bezold-Jarisch; phenyl biguanide; bradycardia; heart; chemoreflex; parasympathetic; vagus; single unit activity



Address for reprint requests and other correspondence: L. Quintin, Dept. of Physiology, CNRS UMR 5123, 8 Rue R Dubois, 69622 Lyon-Villeurbanne, France (e-mail: quintin{at}univ-lyon1.fr)







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