Altered nitric oxide mechanism within the paraventricular nucleus contributes to the augmented carotid body chemoreflex in heart failure

Maram K. Reddy, Harold D. Schultz, Hong Zheng, Kaushik P. Patel

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Our previous study demonstrated a contribution of the paraventricular nucleus (PVN) of the hypothalamus in the processing of the carotid body (CB) chemoreflex. Nitric oxide (NO) (within the PVN), known to modulate autonomic function, is altered in rats with heart failure (HF). Therefore, the goal of the present study was to examine the influence of endogenous and exogenous NO within the PVN on the sympathoexcitatory component of the peripheral chemoreflex in normal and HF states. We measured mean arterial blood pressure, heart rate, renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) in sham-operated and HF rats (6-8 wk after coronary artery ligation) after incremental doses of potassium cyanide (25-100 μg/kg iv). There was potentiation of the reflex responses in HF compared with sham-operated rats. Bilateral microinjection of an inhibitor of NO synthase, NG- monomethyl-L-arginine (50 pmol), into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation in sham-operated rats but had no effect in HF rats. Conversely, bilateral microinjection of a NO donor, sodium nitroprusside (50 nmol), into the PVN attenuated the RSNA response of the peripheral chemoreflex in sham-operated rats but to a smaller extent in HF rats. These data indicate that 1) NO within the PVN plays an important role in the processing of the CB chemoreflex and 2) there is an impairment of the NO function within the PVN of HF rats, which contributes to an augmented peripheral chemoreflex and subsequent elevation of sympathetic activity in HF.

Original languageEnglish (US)
Pages (from-to)H149-H157
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • Hypothalamus
  • Phrenic nerve activity
  • Renal sympathetic nerve activity

ASJC Scopus subject areas

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

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