Stone A J, Copp S W, Kaufman M P
Heart and Vascular Institute, Penn State College of Medicine, Hershey, PA 17033, USA.
Heart and Vascular Institute, Penn State College of Medicine, Hershey, PA 17033, USA.
Neuroscience. 2014 Sep 26;277:26-35. doi: 10.1016/j.neuroscience.2014.06.061. Epub 2014 Jul 5.
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.
先前的研究发现，骨骼肌中的前列腺素在引发运动升压反射中起作用；然而，前列腺素在该反射的脊髓传导中所起的作用尚不清楚。因此，我们确定了脊髓中环氧化酶（COX）活性的阻断和/或内过氧化物（EP）2或4受体的脊髓阻断是否会减弱去大脑大鼠的运动升压反射。我们首先确定，鞘内注射非特异性COX抑制剂酮咯酸（100μg溶于10μl）、COX-2特异性抑制剂塞来昔布（100μg溶于10μl）、EP2拮抗剂PF-04418948（10μg溶于10μl）和EP4拮抗剂L-161,982（4μg溶于10μl）分别有效减弱了对鞘内注射花生四烯酸（100μg溶于10μl）、EP2激动剂布他前列素（4ng溶于10μl）和EP4激动剂TCS 2510（6.25μg溶于2.5μl）的升压反应。一旦确定了有效剂量，我们在鞘内注射酮咯酸、塞来昔布、EP2拮抗剂和EP4拮抗剂前后对后肢进行了静态收缩。我们发现酮咯酸显著减弱了对静态收缩的升压反应（注射酮咯酸前：23±5mmHg，注射酮咯酸后14±5mmHg；p<0.05），而塞来昔布没有效果。我们还发现，8μg的L-161,982而非4μg的L-161,982显著减弱了对静态收缩的升压反应（注射L-161,982前：21±4mmHg，注射L-161,982后12±3mmHg；p<0.05），而PF-04418948（10μg）没有效果。我们得出结论，脊髓中的COX-1而非COX-2在引发运动升压反射中起作用，并且该酶产生的脊髓前列腺素最有可能激活脊髓EP4受体，而非EP2受体。
