Hydrogen Sulfide-Induced Dual Vascular Effect Involves Arachidonic Acid Cascade in Rat Mesenteric Arterial Bed

• Published in: The Journal of pharmacology and experimental therapeutics 2011-04, Vol.337 (1), p.59-64
• Main Authors: d’Emmanuele di Villa Bianca, Roberta, Sorrentino, Rosalinda, Coletta, Ciro, Mitidieri, Emma, Rossi, Antonietta, Vellecco, Valentina, Pinto, Aldo, Cirino, Giuseppe, Sorrentino, Raffaella
• Format: Article
• Language: English
• Subjects: Animals; Arachidonic Acid - physiology; Biological Factors - metabolism; Dose-Response Relationship, Drug; Hydrogen Sulfide - pharmacology; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; Rats; Rats, Wistar; Signal Transduction - drug effects; Signal Transduction - physiology; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasodilation - drug effects; Vasodilation - physiology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.110.176016

Hydrogen sulfide (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 sulfide (NaHS), an H2S donor, on the rat mesenteric arterial bed. NaHS concentration-response curve was performed on preconstricted mesenteric arterial bed. To assess the contribution of EDHF, we performed a pharmacologic dissection using indomethacin, NG-nitro-l-arginine methyl ester (l-NAME), or apamin and charybdotoxin 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 phospholipase A2 (PLA2), lipoxygenase, and cytochrome P450 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 charybdotoxin significantly inhibited NaHS-induced relaxation. Pretreatment 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 cytosolic PLA2 close to the nucleus, which implicates activation of this enzyme. Our data indicate that H2S could activate PLA2, which in turn releases arachidonic acid leading, initially, to vasoconstriction followed by vasodilation mediated by cytochrome P450-derived metabolites. Because EDHF has been presumed to be a cytochrome P450 derivative of the arachidonic acid, our results suggest that H2S acts through EHDF release.