MEDIATION BY PROSTAGLANDINS OF THE NITRIC OXIDE-INDUCED NEUROGENIC VASODILATATION IN RAT SKIN

1 Intraplantar administration of the nitric oxide (NO) donor, sodium n itroprusside (SNP), induces hyperaemia in the rat paw skin, which is i n part due to release of calcitonin gene-related peptide (CGRP) from a fferent nerve fibres. The present study examined whether prostaglandin s or other inflammatory mediators participate in the neurogenic vasodi latation caused by SNP. Blood flow in the plantar hindpaw skin of uret hane-anaesthetized rats was measured by laser Doppler flowmetry. 2 The hyperaemic responses to intraplantar administration of the NO donors SNP (150 pmol) and 3-morpholino-sydnonimine (SIN-1, 15 nmol) were atte nuated by 45% and 61%, respectively, after injection of the CGRP antag onist, CGRP(8-37) (50 nmol kg(-1), i.v.) which did not significantly c hange baseline blood flow. 3 The NO synthase inhibitor N-G-nitro-L-arg inine methyl ester (L-NAME, 15 mg kg(-1) i.v.), the bradykinin antagon ist Hoe-140 (100 nmol kg(-1), i.v.) and the histamine antagonists, pyr ilamine (2 mg kg(-1), i.v.) plus cimetidine (10 mg kg(-1), i.p.) were without effect on baseline blood flow and the vasodilatation caused by SNP. 4 The cyclo-oxygenase inhibitors, indomethacin (10 mg kg(-1), i. p.) and flurbiprofen (5 mg kg(-1), i.p.) depressed the SNP-induced hyp eraemia by 65% and 42%, respectively, without altering baseline blood how. The ability of CGRP(8-37) to inhibit the vasodilator response to SNP was lost in indomethacin-treated rats. 5 Intraplantar administrati on of prostaglandin E(2) (PGE(2), 15 pmol) evoked cutaneous vasodilata tion which was attenuated by 66% after administration of CGRP(8-37) bu t remained unaltered by indomethacin or L-NAME. 6 These data indicate that the neurogenic hyperaemia which in rat skin is induced by intrapl antar administration of NO donors involves the formation of prostaglan dins which in turn cause release of the vasodilator peptide, CGRP, fro m perivascular afferent nerve fibres.