EVIDENCE FOR FUNCTIONAL-RESPONSES TO SENSORY NERVE-STIMULATION OF RATSMALL MESENTERIC VEINS

Sensory C-fibers have been implicated in the control of vascular tone and are believed to be predominantly arteriolar in the microvasculatur e. There have been no direct investigations into the effects of C-fibe r activation in venous microvessels. Therefore, we have investigated t he effects of neuropeptides and activation of sensory C-fibers in rat small mesenteric veins. Small second- or third-order veins were dissec ted from the rat mesentery and mounted in a tension myograph for measu rement of reactivity. Neither substance P or calcitonin gene-related p eptide (CGRP) relaxed precontracted veins. However, substance P caused a concentration-dependent contraction. The curve was shifted to the r ight in a concentration-dependent manner by the tachykinin neurokinin, receptor antagonist RP 67,580 (0.1-1 mu M). To activate sensory C-fib ers, capsaicin was applied. Capsaicin had no contractile activity in t hese vessels but caused concentration-dependent relaxation. This respo nse was significantly attenuated in veins taken from animals in which C-fibers had been largely destroyed (P < .001, n = 5) and in vessels t hat had been pretreated with the vanilloid receptor blocker ruthenium red (P < .01, n = 5). Endothelial denudation (n = 6) also abolished th e response, but the nitric oxide synthase inhibitor N-G-monomethyl-L-a rginine (100 mu M, n = 5) did not inhibit the response; N-omega-nitro- L-arginine methyl ester (100-300 mu M, n = 4) did inhibit the response . The guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin -1-one also significantly attenuated the response (n = 5). The cycloox ygenase inhibitor indomethacin (5 mu M, n = 5) and the CGRP receptor a ntagonist CGRP(8-37) (1 mu M) were without effect. These results demon strate that capsaicin, a selective C-fiber activator, relaxes small ve ins in an endothelium-dependent but CGRP- and substance P-independent manner, and they demonstrate that the venous side of the microcirculat ion responds directly to sensory stimulation.