Regulation of jejunal arterioles by capsaicin-sensitive nerves in Nippostrongylus brasiliensis-sensitized rats.
The mechanisms by which sensory nerves elicit dilation of serosal arterioles in the jejunum of rats sensitized to the nematode Nippostrongylus brasiliensis were studied using intravital microscopy. Capsaicin (0.002-2 micrograms), applied as a bolus topically to the serosa, produced a substantially larger dilation in the sensitized rats than in unsensitized rats. Abolition of the primary afferent nerves by neonatal treatment with capsaicin and blockade of capsaicin with the antagonist ruthenium red reduced markedly the dilator actions of capsaicin. Mast cell products 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 microM) blocked the actions of capsaicin. Neither cyclooxygenase products nor platelet-activating factor was involved in capsaicin-induced dilation. The actions of capsaicin and histamine were mediated via a nitric oxide (NO)-dependent mechanism, because superfusion of an inhibitor of NO synthase (NG-nitro L-arginine methyl ester, 10 microM) blocked their effects. This inhibition of capsaicin-elicited dilation by NG-nitro L-arginine methyl ester was prevented by L-arginine (100 microM), the substrate for NO synthase. Thus the arteriolar dilation evoked by capsaicin activation of primary afferent nerves in N. brasiliensis-sensitized rats involves predominantly the release from mast cells of histamine, which then dilates the vessels by a NO-dependent mechanism.
Mathison
R
R
Department of Medical Physiology, Faculty of Medicine, University of Calgary, Alberta, Canada.
Davison
J S
JS
D000818:Animals; D001160:Arterioles / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D007583:Jejunum / Q000098:blood supply*; D008297:Male; D008407:Mast Cells / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009559:Nippostrongylus / Q000276:immunology*; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide; D006632:Histamine; D002211:Capsaicin