Wilson L B, Hand G A
Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama 36688, USA.
Am J Physiol. 1998 Sep;275(3):H789-96. doi: 10.1152/ajpheart.1998.275.3.H789.
The physiological effects of substance P (SP) are mediated via activation of neurokinin-1 (NK-1) receptors. The purpose of this study was to test the hypothesis that blockade of NK-1 receptors in the dorsal horn, both at the site of entry for the primary afferent neurons and adjacent spinal segments, attenuates the pressor reflex evoked by static contraction and stretch of skeletal muscle. Cats were anesthetized with alpha-chloralose and urethan, and a laminectomy was performed. With the exception of the L7 dorsal root, the dorsal and ventral roots from L5 to S2 were sectioned on one side of the spinal cord. Thus the primary afferent fibers mediating the pressor reflex enter the spinal cord via the L7 dorsal root in these experiments. Based on dose-response data, dialysis of the NK-1 receptor antagonist CP-96,345 (5 mM for 2 h) into the L7 dorsal horn ipsilateral to the contracting muscle attenuated the pressor response to static contraction (75 +/- 15 vs. 46 +/- 7 mmHg; n = 5 cats) but not muscle stretch (60 +/- 12 vs. 50 +/- 8 mmHg). Administration of the inactive enantiomer of CP-96,345, CP-96,344 (5 mM for 2 h), into the L7 dorsal horn failed to alter the cardiovascular changes elicited by contraction (45 +/- 7 vs. 43 +/- 6 mmHg) and stretch (31 +/- 8 vs. 32 +/- 11). Dialysis of 5 mM CP-96, 345 into the dorsal horn at the L6 and S1 segments for 2 h decreased the peak pressor response to static contraction (58 +/- 9 vs. 31 +/- 6 mmHg; n = 7) and muscle stretch (61 +/- 6 vs. 44 +/- 8 mmHg). These data suggest that the activation of NK-1 receptors, both at the site of entry and in regions outside of the entry site for afferent neurons, is involved in the spinal processing that produces the pressor reflex evoked by static contraction of skeletal muscle.
P物质（SP）的生理效应是通过神经激肽-1（NK-1）受体的激活介导的。本研究的目的是检验以下假设：在背角，即在初级传入神经元的进入部位及其相邻的脊髓节段阻断NK-1受体，可减弱由骨骼肌静态收缩和伸展诱发的升压反射。用α-氯醛糖和乌拉坦麻醉猫，并进行椎板切除术。除L7背根外，在脊髓一侧切断L5至S2的背根和腹根。因此，在这些实验中，介导升压反射的初级传入纤维通过L7背根进入脊髓。根据剂量反应数据，将NK-1受体拮抗剂CP-96,345（5 mM，持续2小时）透析到与收缩肌肉同侧的L7背角，可减弱对静态收缩的升压反应（75±15对46±7 mmHg；n = 5只猫），但对肌肉伸展无影响（60±12对50±8 mmHg）。将CP-96,345的无活性对映体CP-96,344（5 mM，持续2小时）注入L7背角，未能改变由收缩（45±7对43±6 mmHg）和伸展（31±8对32±11 mmHg）引起的心血管变化。将5 mM CP-96,345透析到L6和S1节段的背角2小时，可降低对静态收缩（58±9对31±6 mmHg；n = 7）和肌肉伸展（61±6对44±8 mmHg）的峰值升压反应。这些数据表明，在传入神经元的进入部位及其以外的区域，NK-1受体的激活参与了产生由骨骼肌静态收缩诱发的升压反射的脊髓加工过程。
