INFLUENCE OF NK-1 BLOCKADE IN THE DORSAL HORN ON THE EXERCISE PRESSOR REFLEX1017

Abstract

Static contraction and stretch of skeletal muscle elicit reflex increases in cardiovascular function and previous work suggests that SP release in the spinal cord is involved in mediating this reflex. For this study, we tested the following hypotheses: 1) that blockade of SP receptors (NK-1) in the dorsal horn where the afferent neurons enter the spinal cord (L7, see below) attenuates the exercise pressor reflex, and 2) that administration of an antagonist to NK-1 receptors in the dorsal horn of segments adjacent to the site of entry of the afferent neurons (L6 and S1) blunts the reflex responses evoked by static contraction and muscle stretch. Cats were anesthetized with alpha-chloralose (60 mg/kg, i.v.) and urethane (200 mg/kg, i.v.), and a laminectomy was performed to expose the spinal cord. 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 afferent fibers mediating the pressor reflex enter the spinal cord via the L7 dorsal root. Static contraction of the triceps surae muscle was evoked by electrically stimulating the peripheral ends of the L7 and S1 ventral roots. Based upon our dose-response data, 5.0 mM CP-96,345(selective NK-1 antagonist) was dialyzed into the L7 dorsal horn, and this attenuated the pressor response to static contraction (75±15 mmHg vs. 46±7 mmHg; n=5). By contrast, administration of this dose into the L7 dorsal horn had no effect on the blood pressure response elicited by muscle stretch (60±12 mmHg vs. 50±8 mmHg; n=5). Dialysis of 5 mM CP-96,345 into the dorsal horn at the L6 and S1 segments decreased the pressor response to static contraction (58±9 mmHg vs. 31±6 mmHg; n=7), and muscle stretch (61±6 mmHg vs. 44±8 mmHg; n=6). These results support the hypothesis that SP release in the dorsal horn is involved in producing the reflex cardiovascular adjustments evoked by static contraction of skeletal muscle. Further, these data suggest that activation of NK-1 receptors in regions outside of the entry site for the afferent neurons plays a role in the spinal processing that produces the exercise pressor reflex.