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

1 Intraplantar administration of the nitric oxide (NO) donor, sodium nitroprusside (SNP), induces hyperaemia in the rat paw skin, which is in part due to release of calcitonin gene-related peptide (CGRP) from afferent nerve fibres. The present study examined whether prostaglandins or other inflammatory mediators participate in the neurogenic vasodilatation caused by SNP. Blood flow in the plantar hindpaw skin of urethane-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 attenuated by 45% and 61%, respectively, after injection of the CGRP antagonist, CGRP(8-37) (50 nmol kg(-1), i.v.) which did not significantly change baseline blood flow. 3 The NO synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, 15 mg kg(-1) i.v.), the bradykinin antagonist Hoe-140 (100 nmol kg(-1), i.v.) and the histamine antagonists, pyrilamine (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 hyperaemia 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 administration of prostaglandin E(2) (PGE(2), 15 pmol) evoked cutaneous vasodilatation which was attenuated by 66% after administration of CGRP(8-37) but remained unaltered by indomethacin or L-NAME. 6 These data indicate that the neurogenic hyperaemia which in rat skin is induced by intraplantar administration of NO donors involves the formation of prostaglandins which in turn cause release of the vasodilator peptide, CGRP, from perivascular afferent nerve fibres.