Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats

A. J. Stone, S. W. Copp, Marc P Kaufman

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide (EP) 2 or 4 receptors attenuated the exercise pressor reflex in decerebrated rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100. μg in 10. μl), a COX-2-specific inhibitor Celecoxib (100. μg in 10. μl), an EP2 antagonist PF-04418948 (10. μg in 10. μl), and an EP4 antagonist L-161,982 (4. μg in 10. μl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100. μg in 10. μl), EP2 agonist Butaprost (4. ng in 10. μl), and EP4 agonist TCS 2510 (6.25. μg in 2.5. μl), respectively. Once effective doses were established, we statically contracted the hind limb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23 ± 5. mmHg, after Ketorolac 14 ± 5. mmHg; p<. 0.05) whereas Celecoxib had no effect. We also found that 8. μg of L-161,982, but not 4. μg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21 ± 4. mmHg, after L-161,982 12 ± 3. mmHg; p<. 0.05), whereas PF-04418948 (10. μg) had no effect. We conclude that spinal COX-1, but not COX-2, plays a role in evoking the exercise pressor reflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors.

Original languageEnglish (US)
Pages (from-to)26-35
Number of pages10
JournalNeuroscience
Volume277
DOIs
StatePublished - Sep 26 2014
Externally publishedYes

Keywords

  • Cyclooxygenase
  • Endoperoxide receptors
  • Static contraction
  • Sympathetic nervous system
  • Thin fiber muscle afferents

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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