Intrathecal orexin A increases sympathetic outflow and respiratory drive, enhances baroreflex sensitivity and blocks the somato-sympathetic reflex

I. Z. Shahid, A. A. Rahman, P. M. Pilowsky

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

BACKGROUND Intrathecal (i.t.) injection of orexin A (OX-A) increases blood pressure and heart rate (HR), but the effects of OX-A on sympathetic and phrenic, nerve activity, and the baroreflex(es), somato-sympathetic and hypoxic chemoreflex(es) are unknown. Experimental Approach Urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats were examined in this study. The effects of i.t. OX-A (20 nmol 10 ÂμL -1) on cardiorespiratory parameters, and responses to stimulation of the sciatic nerve (electrical), arterial baroreceptors (phenylephrine hydrochloride, 0.01 mg kg -1 i.v.) and peripheral (hypoxia) chemoreceptors were also investigated. Key Results i.t. OX-A caused a prolonged dose-dependent sympathoexcitation, pressor response and tachycardia. The peak effect was observed at 20 nmol with increases in mean arterial pressure, HR and splanchnic sympathetic nerve activity (sSNA) of 32 mmHg, 52 beats per minute and 100% from baseline respectively. OX-A also dose-dependently increased respiratory drive, as indicated by a rise in phrenic nerve amplitude and a fall in phrenic nerve frequency, an increase in neural minute ventilation, a lengthening of the expiratory period, and a shortening of the inspiratory period. All effects of OX-A (20 nmol) were attenuated by the orexin receptor 1 antagonist SB 334867. OX-A significantly reduced both sympathoexcitatory peaks of somato-sympathetic reflex while increasing baroreflex sensitivity. OX-A increased the amplitude of the pressor response and markedly amplified the effect of hypoxia on sSNA. Conclusions Thus, activation of OX receptors in rat spinal cord alters cardiorespiratory function and differentially modulates sympathetic reflexes.

Original languageEnglish
Pages (from-to)961-973
Number of pages13
JournalBritish Journal of Pharmacology
Volume162
Issue number4
DOIs
Publication statusPublished - Feb 2011

Keywords

  • baroreflex
  • hypoxia
  • Orexin A
  • phrenic nerve discharge
  • somato-sympathetic reflex
  • sympathetic nerve activity

Fingerprint Dive into the research topics of 'Intrathecal orexin A increases sympathetic outflow and respiratory drive, enhances baroreflex sensitivity and blocks the somato-sympathetic reflex'. Together they form a unique fingerprint.

Cite this