Interaction between sympathetic and sensory nerves in rat small arteries: involvement of nitric oxide

The aim of this study was to determine the effects of C-fiber activation on the reactivity of resistance arteries. Rat small mesenteric arteries were mounted in a tension myograph. Electrical field stimulation (EFS) of vessels produced brief contractions that were abolished by tetrodotoxin (1 microM, n = 4) or guanethidine (5 microM, n = 4). Capsaicin caused concentration-related attenuation of the EFS contraction [giving EFS responses of 61.7 +/- 4.3, 39.8 +/- 5.9, and 14.0 +/- 3.9% (n = 13-16) of control EFS contraction in the presence of 1, 3, and 10 microM capsaicin, respectively]. This effect was attenuated by the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (1 microM, n = 4, P < 0.05), NG-monomethyl-L-arginine (L-NMMA; 100 microM, n = 4, P < 0.01), or endothelial denudation (n = 5, P < 0.001). CGRP concentration-dependent inhibited (n = 5) EFS contraction, but this was unaffected by (L-NMMA (100 microM, n = 4). Capsaicin also relaxed preconstricted vessels (U-46619). This response was attenuated by ruthenium red (30 microM, n = 5, concentration ratio of 3.5 +/- 1.0) and CGRP-(8-37) (1 microM, n = 5, P < 0.05), while L-NMMA (100 microM, n = 6) showed variable effects, and denudation had no effect. These results show directly for the first time responses to activation of capsaicin-sensitive C fibers which modulate reactivity and the responses to sympathetic stimulation of isolated rat small mesenteric arteries, with the latter being an endothelial nitric oxide-dependent effect.