Corticotropin-releasing hormone causes vasodilation in human skin via mast cell-dependent pathways.
CRH plays a central role as a mediator of the hypothalamic-pituitary-adrenal axis and stress response and is a potent vasodilator. Previously, we have shown that CRH causes a gender-specific vasodilation in human skin, although the mechanism by which CRH operates is unclear. CRH causes mast cell degranulation in rat skin. As such, histamine and other mast cell-derived factors may be indirectly responsible for the vasodilatory effects of CRH, although CRH is also known to act directly on the vasculature. CRH-induced vasodilation in human skin was examined using laser Doppler flowmetry and iontophoresis in adult females. CRH (1 nM) was administered iontophoretically to the forearm, and blood flow was measured simultaneously in the same area by laser Doppler. CRH-induced dilation of the skin microvasculature was significantly reduced in the presence of the mast cell degranulation inhibitor, sodium cromoglycate, the histamine H(1)-antagonist, promethazine, or the H(2)-antagonist, ranitidine. CRH-induced dilation was also significantly reduced in the presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester, or the cyclooxygenase inhibitor, piroxicam. These findings provide novel evidence that CRH-induced vasodilation in human skin occurs via mast cell degranulation and is principally mediated by histamine and, to a lesser extent, by prostacyclin and nitric oxide.
Crompton
Renee
R
Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle NSW, Australia.
Clifton
Vicki L
VL
Bisits
Andrew T
AT
Read
Mark A
MA
Smith
Roger
R
Wright
Ian M R
IM
D015550:Cell Degranulation / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage; D006801:Humans; D008407:Mast Cells / Q000502:physiology*; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009599:Nitroprusside / Q000008:administration & dosage; D011398:Promethazine / Q000008:administration & dosage; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage
D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D018019:Receptors, Corticotropin-Releasing Hormone; D014665:Vasodilator Agents; D009599:Nitroprusside; D003346:Corticotropin-Releasing Hormone; D011398:Promethazine; D019331:NG-Nitroarginine Methyl Ester