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The rat hind-limb vasculature releases substance P when subjected to a rapid increase in flow through the vascular bed. This release also occurs during high flow after rats have been capsaicinized, when loss of substance P-containing nerve fibers was verified by immunohistochemistry. Air treatment, a procedure shown by transmission electron microscopy to have removed endothelial cells from the arteries but not arterioles or capillaries of the hind-limb preparations, eliminated this release. Thus, the substance P released is unlikely to arise from perivascular nerves but rather from arterial endothelial cells.

Substance P is released from the endothelium of normal and capsaicin-treated rat hind-limb vasculature, in vivo, by increased flow.