Tachykinin-induced vasodilatation in rat skin measured with a laser-Doppler flowmeter: evidence for receptor-mediated effects.

Vasodilatation was induced by perfusion of the tachykinins substance P (SP), neurokinin A and neurokinin B and the analogues [Glp6, D-Pro9]SP-(6-11) and [Glp6, L-Pro9]SP-(6-11) over the base of vacuum-induced blisters on the rat footpad. Vasodilatation was measured as change in blood flow using a laser-Doppler flowmeter. The tachykinins induced vasodilatation in a dose-response manner with a threshold of approximately 3 pmol and pD2's of 6.48, 6.13 and 6.21 for SP, neurokinin A and neurokinin B respectively. The D- and L-Pro analogues of [Glp6, Pro9]SP-(6-11) also induced vasodilatation in a dose-dependent manner. The L-Pro analogue was more potent than the D-Pro analogue (D/L ratio of the EC50's = 21) which suggests the involvement of an NK-1 type receptor in the mediation of small vessel vasodilatation. The vasodilatation to SP was reduced by 64% and 59% in capsaicin- and antihistamine-pretreated animals respectively, demonstrating the involvement of capsaicin-sensitive primary afferent nerves and mast cells in the vasodilatation component of the neurogenic inflammatory response.