Segmental effect of spinal NK-1 receptor blockade on the pressor reflex.
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.
Department of Physiology, University of South Alabama College of Medicine, Mobile, Alabama 36688, USA.
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D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000502:physiology*; D002415:Cats; D005260:Female; D007796:Laminectomy; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000502:physiology / Q000601:surgery
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; C066892:CP 96345