Effect of systemic B-type natriuretic peptide on cardiac vagal motoneuron activity

Abstract

Toader E, McAllen RM, Cividjian A, Woods RL, Quintin L. Effect of systemic B-type natriuretic peptide on cardiac vagal motoneuron activity. Am J Physiol Heart Circ Physiol 293: H3465-H3470, 2007. First published September 28, 2007; doi:10.1152/ajpheart.00528.2007.-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 g to evoke the von Bezold-Jarisch reflex, caused a dose-related increase in CVM activity and bradycardia. BNP infusion (25 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 iv) significantly enhanced both the CVM response to PBG (n ϭ 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 INCREASED SYMPATHETIC DRIVE and reduced vagal activity are prognostic of a poor outcome in cardiovascular disease (12,14,29). Many studies have shown the benefits of reducing sympathetic activity in cardiovascular disease (10), but actions on the vagal arm of autonomic nervous system have been underexploited. It is likely that enhancing vagal drive to the heart will be beneficial because efferent vagal stimulation can improve the outcome after myocardial infarction in dogs (29). Mechanisms that may enhance vagal tone are therefore of interest for their therapeutic potential in cardiovascular disease.The cardiac natriuretic peptides-atrial natriuretic peptide (ANP), B-and C-type natriuretic peptides (BNP and CNP)-have actions that may be interpreted as cardioprotective (31). Indeed, BNP (Nesiritide) has proved clinically useful in the treatment of congestive heart failure (5, 16). One of these presumed cardioprotective actions is to enhance bradycardic reflexes such as the von Bezold-Jarisch (cardiopulmonary) ch...

Cardiovascular Autonomic Dysfunction in Chronic Kidney Disease: a Comprehensive Review

“…Studies suggest a critical role for ANP in inhibiting hypothalamic NE release [154,155] and enhancing cardiac vagal baroreflex and cardiopulmonary reflex function [156,157], suggesting a potential role for ANP in modulating autonomic function. In the SHR, ANPmediated facilitation of cardiac baroreflex is absent, indicating altered ANP-ANS interaction during disease [157,158].…”

Cardioinhibitory actions of clonidine assessed by cardiac vagal motoneuron recordings

“…If an increased routine for CVM recording leads to higher success rate, the present model will allow pharmacological investigation. For example, B-natriuretic peptide increases CVM activity during von Bezold-Jarisch reflex [47]. Also, some drugs increase the slope of the cardiac baroreflex (see Introduction).…”

Restorative Effect of Atrial Natriuretic Peptide or Chronic Neutral Endopeptidase Inhibition on Blunted Cardiopulmonary Vagal Reflexes in Aged Rats

“…Interestingly, we recently found that under similar conditions, BNP infusion in young adult Wistar rats enhanced the BJR, yet had no effect on vagal efferent responsiveness. 28 Because additional ANP restored the vagal reflex deficit in old rats, we considered the hypothesis that normal circulating levels of ANP may decline with age. However, as other studies have shown in different rat strains, 21,29 and indeed in humans, 30,31 plasma ANP levels in old Munich-Wistar rats were increased approximately 2-fold compared with younger rats.…”