Investigation of 6-hydroxydopamine-induced plasma extravasation in rat skin

Abstract

Perfusion of 6-hydroxydopamine into the rat knee and trachea induces plasma extravasation, possibly by tissue-specific mechanisms involving sympathetic and sensory nerves respectively, and we aimed to identify the mediators which contribute to this response in skin. 6-Hydroxydopamine (both hydrobromide and hydrochloride salts), dose dependently increased plasma extravasation into rat dorsal skin, however, when compared to bradykinin or the tachykinin NK 1 receptor agonist GR73632, high concentrations of 6-hydroxydopamine (1–10 μmol/site) were required. The response to 6-hydroxydopamine was not inhibited in chemically sympathectomised rats (6-hydroxydopamine, 300 mg/kg i.p. over 7 days) but was significantly reduced by co-administration with the histamine (H 1) and the 5-HT receptor antagonists mepyramine and methysergide and in skin sites pre-injected with compound 48 80 (4 μg, −18 h) to degranulate dermal mast cells. The response was not inhibited by co-injection of the tachykinin NK 1 receptor antagonist SR140333 or by the cyclo-oxygenase inhibitor indomethacin (5 mg kg −1 i.p., −30 min) except at the lowest dose of 6-hydroxydopamine (1 μmol/site). We conclude that 6-hydroxydopamine is not a potent or selective mediator of increased vascular permeability in rat skin but, at high concentrations, may induce oedema formation via release of vasoactive amines from mast cells, augmented by generation of prostaglandins.