ATTENUATION OF THE REFLEX RESPONSES TO MUSCLE-CONTRACTION BY THE COADMINISTRATION OF ANTAGONISTS TO SUBSTANCE-P AND SOMATOSTATIN INTO THE DORSAL HORN

Objective: The aim was to determine if the coadministration of antagon ists to substance P and somatostatin into the L(7) dorsal horn blunts the reflex cardiovascular responses to static contraction to a greater extent than each antagonist alone. The possibility that this attenuat ion is mediated by blunting the contraction evoked increases in sympat hetic outflow was also tested. Methods: Using alpha chloralose anaesth etised cats (n = 8), static contraction and stretch of the triceps sur ae muscle were performed before and after microinjecting (1 mu l) 250 ng of the substance P antagonist, D-Pro(2)-D-Phe(7)-D-Trp(9)-substance P, and the somatostatin antagonist, henylaIanyl-D-tryptophyl-lysyl-th reonyl-[benzyl]). The muscle was contracted by electrically stimulatin g the peripheral end of the cut L(7) ventral root. Results: Before inj ecting the antagonists, static muscle contraction increased mean arter ial blood pressure by 40(SEM 6) mm Hg, heart rate by 13(2) beats.min(- 1) and renal sympathetic nerve activity (RSNA) by 41(7)%. These change s were blunted by the antagonists since the increases in blood pressur e, heart rate, and RSNA were reduced to 21(3) mm Hg, 8(1) beats.min(-1 ), and 23(5)%, respectively. In contrast, antagonist administration di d not affect the presser 1:33(5) v 31(5) mm Hgl, heart rate [9(2) v 10 (2) beats.min(-1)], or RSNA [23(4)% v 25(5)%] responses to muscle stre tch. Microinjection of 2% lignocaine into the dorsal horn virtually ab olished the reflex changes elicited by muscle stretch. Conclusions: Th e release of substance P and somatostatin in the spinal cord plays a r ole in mediating the cardiovascular changes caused by static contracti on, but the release of other neuro transmitters/neuromodulators is als o involved. The attenuation produced by these antagonists is mediated, at least in part, by reducing sympathetic outflow.