RT Journal Article
SR Electronic
T1 Hydrogen sulphide induced-dual vascular effect involves arachidonic acid cascade in rat mesenteric arterial bed
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.110.176016
DO 10.1124/jpet.110.176016
A1 Roberta d'Emmanuele di Villa Bianca
A1 Rosalinda Sorrentino
A1 Ciro Coletta
A1 Emma Mitidieri
A1 Antonietta Rossi
A1 Valentina Vellecco
A1 Aldo Pinto
A1 Giuseppe Cirino
A1 Raffaella Sorrentino
YR 2011
UL http://jpet.aspetjournals.org/content/early/2011/01/11/jpet.110.176016.abstract
AB Hydrogen sulphide (H2S), a novel gaseous transmitter, is considered a physiological regulator of vascular homeostasis. Recent evidence suggests H2S as an endothelium hyperpolarizing factor (EDHF) candidate. To address this issue, we evaluated the vascular effect of sodium hydrogen sulphide (NaHS), an H2S donor on the rat mesenteric arterial bed. NaHS concentration-response curve was performed on pre-constricted mesenteric arterial bed. In order to asses the contribute of EDHF, we performed a pharmacological dissection using indomethacin, NG-nitro-L-arginine methyl ester (L-NAME) or apamin and charibdotoxin, as cyclooxygenase, nitric oxide-synthase and calcium-dependent potassium channel inhibitors, respectively. In another set of experiments we used 4-(4-Octadecylphenyl)-4-oxobutenoic acid, baicalein or proadifen as PLA2, lipoxygenase and P450 cytochrome inhibitors respectively. Finally, an immunofluorescence study was performed to support the involvement of PLA2 in mesenteric artery challenged by NaHS. NaHS promoted a dual vascular effect, i.e., vasoconstriction and vasodilation. L-NAME or baicalein administration affected neither NaHS-mediated vasodilation nor vasoconstriction, whereas apamin and charibdotoxin significantly inhibited NaHS-induced relaxation. Pre-treatment with PLA2 inhibitor abolished both the contracting and the relaxant effect, whereas P450 cytochrome blocker significantly reduced NaHS-mediated relaxation. The immunofluorescence study showed that NaHS caused a migration of cPLA2 close to the nucleus, which implies activation of this enzyme. Our data indicate that H2S could activate PLA2 that in turn releases arachidonic acid leading, initially, to vasoconstriction followed by vasodilation mediated by cytochrome P450-derived metabolites. Since EDHF has been presumed to be a cytochrome P450 derivative of the arachidonic acid, our results suggest that H2S acts through EHDF release.