REGULATION OF JEJUNAL ARTERIOLES BY CAPSAICIN-SENSITIVE NERVES IN NIPPOSTRONGYLUS BRASILIENSIS-SENSITIZED RATS

The mechanisms by which sensory nerves elicit dilation of serosal arte rioles in the jejunum of rats sensitized to the nematode Nippostrongyl us brasiliensis were studied using intravital microscopy. Capsaicin (0 .002-2 mu g), applied as a bolus topically to the serosa, produced a s ubstantially larger dilation in the sensitized rats than in unsensitiz ed rats. Abolition of the primary afferent nerves by neonatal treatmen t with capsaicin and blockade of capsaicin with the antagonist rutheni um red reduced markedly the dilator actions of capsaicin. Mast cell pr oducts are important in the actions of capsaicin, because pretreatment with dexamethasone (4 mg/kg), to eliminate mast cells by a macrophage -dependent mechanism, abrogated the actions of capsaicin. In addition, superfusion of the H1 receptor antagonist diphenhydramine (2 mu M) bl ocked the actions of capsaicin. Neither cyclooxygenase products nor pl atelet-activating factor was involved in capsaicin-induced dilation. T he actions of capsaicin and histamine were mediated via a nitric oxide (NO)-dependent mechanism, because superfusion of an inhibitor of NO s ynthase (N-G-nitro L-arginine methyl ester, 10 mu M) blocked their eff ects. This inhibition of capsaicin-elicited dilation by N-G-nitro L-ar ginine methyl ester was prevented by L-arginine (100 mu M), the substr ate for NO synthase. Thus the arteriolar dilation evoked by capsaicin activation of primary afferent nerves in N. brasiliensis-sensitized ra ts involves predominantly the release from mast cells of histamine, wh ich then dilates the vessels by a NO-dependent mechanism.