SEGMENTAL EFFECT OF SPINAL NK-1 RECEPTOR BLOCKADE ON THE PRESSOR REFLEX

The physiological effects of substance P (SP) are mediated via activat ion of neurokinin-1 (NK-I) receptors. The purpose of this study was to test the hypothesis that blockade of NK-1 receptors in the dorsal hor n, both at the site of entry for the primary afferent neurons and adja cent spinal segments, attenuates the presser reflex evoked by static c ontraction and stretch of skeletal muscle. Cats were anesthetized with ol-chloralose and urethan, and a laminectomy was performed. With the exception of the L-7 dorsal root, the dorsal and ventral roots from L- 5 to S-2 were sectioned on one side of the spinal cord. Thus the prima ry afferent fibers mediating the presser reflex enter the spinal cord via the L-7 dorsal root in these experiments. Based on dose-response d ata, dialysis of the NK-I receptor antagonist CP-96,345 (5 mM for 2 h) into the L-7 dorsal horn ipsilateral to the contracting muscle attenu ated the presser response to static contraction (15 +/- 15 vs. 46 +/- 7 mmHg; n = 5 cats) but not muscle stretch (60 +/- 12 vs. 50 +/- 8 mmH g). Administration of the inactive enantiomer of CP-96,345, CP-96,344 (5 mM for 2 h), into the L-7 dorsal horn failed to alter the cardiovas cular 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 L-6 and S-1 segments for 2 h decreased the peak pr esser 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 presser reflex evoked by s tatic contraction of skeletal muscle.