Intrathecal PACAP-38 causes prolonged widespread sympathoexcitation via a spinally mediated mechanism and increases in basal metabolic rate in anesthetized rat

Melissa A. Inglott, Melissa M. J. Farnham, Paul M. Pilowsky

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Abstract

The rostral ventrolateral medulla differentially regulates sympathetic output to different vascular beds, possibly through the release of various neurotransmitters and peptides that may include pituitary adenylate cyclase-activating polypeptide (PACAP). An intrathecal administration of PACAP increases splanchnic sympathetic nerve activity and heart rate, but not mean arterial blood pressure. The mechanism behind this response is unknown but may be due to a differential control of sympathetic outflows. In this study we sought 1) to investigate whether intrathecal PACAP differentially affects sympathetic outflow, 2) to determine whether the intrathecal responses to PACAP are solely due to a spinally mediated mechanism, and 3) to determine whether intrathecal PACAP affects metabolic function. Experiments using urethaneanesthetized, vagotomized, ventilated, and paralyzed adult male Sprague-Dawley rats were conducted in this study. Intrathecal injections of PACAP-38 were given, and mean arterial pressure, heart rate, the activity of regional sympathetic nerves, end-tidal CO2, and core temperature were recorded. The novel findings of this study are that 1) intrathecal PACAP-38 causes a prolonged widespread sympathoexcitation in multiple sympathetic beds, 2) this widespread sympathoexcitation is mediated within the spinal cord itself since spinal transaction does not abrogate the response, and 3) that intrathecal PACAP-38 increases basal metabolic rate. Therefore, we conclude that intrathecal PACAP acts in the spinal cord to cause a prolonged widespread sympathoexcitation and that PACAP also causes an increase in basal metabolic rate that includes an increase in brown adipose tissue thermogenesis in our rat preparation.

Original languageEnglish
Pages (from-to)H2300-H2307
Number of pages8
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume300
Issue number6
DOIs
Publication statusPublished - Jun 2011

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Keywords

  • Blood pressure
  • Metabolism
  • Pituitary adenylate cyclase-activating polypeptide
  • Spinal cord
  • Spinal transection
  • Sympathetic beds

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