Evidence of a role for NK1 and CGRP receptors in mediating neurogenic vasodilatation in the mouse ear.
The aims of this study were to develop a technique to measure blood flow in the mouse ear and to investigate the nature of the vasodilator mediator(s) involved in the response to capsaicin. The response to capsaicin, applied topically, was investigated in anaesthetized CD1 or Sv129+C57BL/6 wild-type (+/+) or NK(1) receptor knockout mice (-/-). Blood flow was assessed by laser Doppler flowmetry and oedema formation by (125)I-albumin accumulation. Capsaicin induced significant increases in blood flow (0.2 - 200 microg in 20 microl) and oedema (2 - 200 microg in 20 microl). The oedema response was absent in NK(1)-/- mice and NK(1)+/+mice treated with the selective NK(1) receptor antagonist SR140333 (480 nmol kg(-1)) as expected. Furthermore, the capsaicin-evoked increase in blood flow was significantly potentiated in the knockout mice (203% of wild-type response, P<0.05) and wild-type mice treated with SR140333 (201%, P<0.05). The CGRP receptor antagonist CGRP(8 - 37) (400 nmol kg(-1)) had no effect on capsaicin-induced blood flow in NK(1)+/+mice but abolished the increased blood flow to capsaicin in NK(1)-/-, and NK(1)+/+wild-type mice pre-treated with SR140333. The results indicate that neurogenic vasodilatation can be measured in the mouse ear. The capsaicin-induced increased blood flow involves activation of, and possible interactions between, both NK(1) and CGRP(1) receptors.
Grant
Andrew D
AD
Centre for Cardiovascular Biology and Medicine, New Hunt's House, Guy's Campus, King's College, London, SE1 1UL.
Gerard
Norma P
NP
Brain
Susan D
SD
D000818:Animals; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000098:blood supply* / Q000294:innervation; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064729:Neurokinin-1 Receptor Antagonists; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D018015:Receptors, Calcitonin Gene-Related Peptide; D018040:Receptors, Neurokinin-1; D002211:Capsaicin