Abstract
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 μM). 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 inhibitorN G-monomethyl-l-arginine (100 μM, n = 5) did not inhibit the response;N ω-nitro-l-arginine methyl ester (100–300 μM, 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 μM, n = 5) and the CGRP receptor antagonist CGRP8–37 (1 μM) 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.
Footnotes
-
Send reprint requests to: Dr. Amrita Ahluwalia, Centre for Clinical Pharmacology, The Rayne Institute, University College London, 5 University St., London WC1E 6JJ, UK.
-
↵1 This work and A.A. were supported by The Wellcome Trust.
- Abbreviations:
- CGRP
- calcitonin gene-related peptide
- l-NAME
- N ω-nitro-l-arginine methyl ester
- NK
- neurokinin
- l-NMMA
- N G-monomethyl-l-arginine
- NO
- nitric oxide
- ODQ
- 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one
- SP
- substance P
- Received April 18, 1996.
- Accepted December 6, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|