Evidence for functional responses to sensory nerve stimulation of rat small mesenteric veins

Sensory C-fibers have been implicated in the control of vascular tone and are believed to be predominantly arteriolar in the microvasculature. There have been no direct investigations into the effects of C-fiber activation in venous microvessels. Therefore, we have investigated the effects of neuropeptides and activation of sensory C-fibers in rat small mesenteric veins. Small second- or third-order veins were dissected from the rat mesentery and mounted in a tension myograph for measurement of reactivity. Neither substance P or calcitonin gene-related peptide (CGRP) relaxed precontracted veins. However, substance P caused a concentration-dependent contraction. The curve was shifted to the right in a concentration-dependent manner by the tachykinin neurokinin1 receptor antagonist RP 67,580 (0.1-1 microM). To activate sensory C-fibers, capsaicin was applied. Capsaicin had no contractile activity in these vessels but caused concentration-dependent relaxation. This response was significantly attenuated in veins taken from animals in which C-fibers had been largely destroyed (P < .001, n = 5) and in vessels that had been pretreated with the vanilloid receptor blocker ruthenium red (P < .01, n = 5). Endothelial denudation (n = 6) also abolished the response, but the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (100 microM, n = 5) did not inhibit the response; N(omega)-nitro-L-arginine methyl ester (100-300 microM, 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 cyclooxygenase inhibitor indomethacin (5 microM, n = 5) and the CGRP receptor antagonist CGRP(8-37) (1 microM) were without effect. These results demonstrate that capsaicin, a selective C-fiber activator, relaxes small veins in an endothelium-dependent but CGRP- and substance P-independent manner, and they demonstrate that the venous side of the microcirculation responds directly to sensory stimulation.