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

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 (100μg in 10μl), a COX-2-specific inhibitor Celecoxib (100μg in 10μl), an EP2 antagonist PF-04418948 (10μg in 10μl), and an EP4 antagonist L-161,982 (4μg in 10μl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100μg in 10μl), EP2 agonist Butaprost (4ng in 10μl), and EP4 agonist TCS 2510 (6.25μg in 2.5μl), 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±5mmHg, after Ketorolac 14±5mmHg; p<0.05) whereas Celecoxib had no effect. We also found that 8μg of L-161,982, but not 4μg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21±4mmHg, after L-161,982 12±3mmHg; p<0.05), whereas PF-04418948 (10μg) 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.