Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS at1 receptors in heart failure

Wei Zhong Wang, Lie Gao, Han Jun Wang, Irving H. Zucker, Wei Wang

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Several sympathoexcitatory reflexes, such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF and to further identify the involvement of angiotensin II type 1 receptors (AT1Rs) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham-operated rats after either chemical or electrical activation of the CSAR. The inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham-operated rats. Bilateral NTS injection of the AT1R antagonist losartan (10 and 100 pmol) dosedependently decreased basal sympathetic nerve activity in CHF but not in sham-operated rats. This procedure also abolished the CSAR-induced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following the stimulation of the CSAR in sham-operated and CHF rats, whereas CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham-operated rats. Finally, the protein expression of AT1R in the NTS was significantly higher in CHF than in sham-operated rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT1R-dependent mechanism.

Original languageEnglish (US)
Pages (from-to)H1216-H1226
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume295
Issue number3
DOIs
StatePublished - Sep 2008

Keywords

  • Angiotensin II type 1 receptor
  • Extracellular recording
  • Microinjection
  • Nucleus of tractus solitarius
  • Sympathetic activity
  • Sympathoexcitatory reflexes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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