AT1 receptor in paraventricular nucleus mediates the enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure

Han Jun Wang, Feng Zhang, Ying Zhang, Xing Ya Gao, Wei Wang, Guo Qing Zhu

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Our previous studies have shown that the cardiac sympathetic afferent reflex (CSAR) was enhanced in the chronic heart failure in dogs and rats. Exogenous angiotensin II (Ang II) in the paraventricular nucleus (PVN) potentiated this reflex which was mediated by AT1 receptor. The aim of the present study was to determine if the abnormal endogenous Ang II and AT1 receptor in the PVN were responsible for the enhanced CSAR in rats with coronary ligation-induced chronic heart failure (CHF). Under urethane and α-chloralose anesthesia, mean arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded in sino-aortic denervated and cervical vagotomized CHF and sham-operated rats. The effects of bilateral microinjection of AT1 receptor antagonist losartan and angiotensin converting enzyme inhibitor captopril on the CSAR evoked by epicardial application of bradykinin (BK, 0.04 and 0.4 μg) were determined respectively. Both AT1 receptor mRNA and AT1 receptor protein in the PVN were measured. Bilateral microinjection of either captopril (10 nmol) or losartan (50 nmol) into the PVN inhibited the enhanced CSAR evoked by BK in rats with CHF, but had no significant effects in sham-operated rats. AT1 receptor protein in the PVN significantly increased in CHF rats compared with sham-operated rats. These results indicated that either decrease of Ang II or blockage of AT1 receptor in the PVN normalized the enhanced CSAR evoked by epicardial application of BK in rats with CHF, and that increased expression of AT1 receptor in the PVN contributed to the enhanced CSAR in the CHF state.

Original languageEnglish (US)
Pages (from-to)56-63
Number of pages8
JournalAutonomic Neuroscience: Basic and Clinical
Volume121
Issue number1-2
DOIs
StatePublished - Aug 31 2005

Keywords

  • AT receptor
  • Angiotensin II
  • Cardiac sympathetic afferent reflex
  • Chronic heart failure
  • Paraventricular nucleus
  • Sympathetic nerve activity

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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