Cyclooxygenase products mediate the cutaneous vasodilation induced by endothelin-1 in humans.
Intradermal injection of endothelin-1 (ET-1) causes vasoconstriction (pallor) at the injection site, surrounded by a larger area of vasodilation (flare) in humans. Some of the vasomotor responses to ET-1 are thought to be mediated by prostaglandins. In the present study, we investigated the involvement of cyclooxygenase-derived products of arachidonic acid metabolism on the cutaneous vasomotor responses to ET-1. Ten normal subjects (25-44 years) were studied after treatment with either indomethacin (50 mg t.i.d.) or placebo according to a double blind cross-over design. Five doses of ET-1 (5 x 10(-5) to 5 x 10(-1) pmol) were injected intradermally 2 h after the last dose of indomethacin or placebo. Pallor and flare areas measured by planimetry 15 min after the injection were analyzed to evaluate cutaneous vasomotor responses to ET-1. ET-1 induced dose-dependent pallor and flare responses that were significant at the dose of 5 x 10(-3) pmol or greater. Indomethacin did not affect the ET-1-induced pallor but significantly shifted to the right the flare dose-response curve to ET-1. The inhibition of the flare response to 5 x 10(-1) pmol ET-1 was 58.9 +/- 8.5%. These results indicate that the cutaneous vasodilation induced by intradermal injection of ET-1 is mediated by the release of vasodilating cyclooxygenase products.
Di Maria
G U
GU
Institute of Respiratory Disease, University of Catania, Italy.
Bellofiore
S
S
Puglisi
S
S
Novo
S
S
Ricciardolo
F L
FL
Mistretta
A
A
D000328:Adult; D016718:Arachidonic Acid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007271:Injections, Intradermal; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D016232:Endothelins; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin