Activity and expression of the vanilloid receptor 1 (TRPV1) is altered by long-term diabetes in epineurial arterioles of the rat sciatic nerve.
BACKGROUND
Epineurial arterioles of the sciatic nerve are innervated by sensory nerves containing calcitonin gene-related peptide (CGRP). We postulated that treating these resistance vessels with capsaicin would cause the release of endogenous CGRP and vascular relaxation.


METHODS
Videomicroscopy was used to examine the effect of capsaicin and neuropeptides on vascular reactivity of epineurial arterioles from control and streptozotocin-induced diabetic rats. Using immunohistochemistry, we examined expression of neuropeptide Y (NPY) and vanilloid receptor 1 in epineurial arterioles.


RESULTS
Instead of relaxation, capsaicin was found to cause a concentration-dependent vasoconstriction in epineurial arterioles. The effect of capsaicin was transient, refractory, blocked by capsazepine and duplicated by resiniferatoxin. When examining potential candidates for the mediation of capsaicin-induced constriction, we found that vasopressin (VP), NPY, serotonin (5HT) and endothelin (ET), but not neurokinin A or substance P, caused a concentration-dependent vasoconstriction of epineurial arterioles. Epineurial arterioles express NPY and receptor antagonists to NPY significantly decreased capsaicin-induced vasoconstriction. In long-term diabetic rats, vasoconstriction to capsaicin was significantly attenuated. However, long-term diabetes did not impair vasoconstriction of epineurial arterioles to exogenous VP, NPY, 5HT or ET. Examining the expression of vanilloid receptor 1 in epineurial arterioles from control and long-term diabetic rats, we found that immunoreactivity for vanilloid receptor 1 was decreased by diabetes.


CONCLUSIONS
These studies suggest that long-term diabetes causes vascular dysfunction in epineurial arterioles of the sciatic nerve that includes a decrease in capsaicin-induced vasoconstriction that is likely due to a decrease in the expression of vanilloid receptor 1.
Davidson
Eric P
EP
Veteran Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, 52246, USA.
Coppey
Lawrence J
LJ
Yorek
Mark A
MA
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002211:Capsaicin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D018715:Microscopy, Video; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000098:blood supply*; D050916:TRPV Cation Channels / Q000235:genetics / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D002211:Capsaicin