title: Hydrogen sulfide dilates cerebral arterioles by activating smooth muscle cell plasma membrane KATP channels.
abstract: Hydrogen sulfide (H(2)S) is a gaseous signaling molecule that appears to contribute to the regulation of vascular tone and blood pressure. Multiple potential mechanisms of vascular regulation by H(2)S exist. Here, we tested the hypothesis that piglet cerebral arteriole smooth muscle cells generate ATP-sensitive K(+) (K(ATP)) currents and that H(2)S induces vasodilation by activating K(ATP) currents. Gas chromatography/mass spectrometry data demonstrated that after placing Na(2)S, an H(2)S donor, in solution, it rapidly (1 min) converts to H(2)S. Patch-clamp electrophysiology indicated that pinacidil (a K(ATP) channel activator), Na(2)S, and NaHS (another H(2)S donor) activated K(+) currents at physiological steady-state voltage (-50 mV) in isolated cerebral arteriole smooth muscle cells. Glibenclamide, a selective K(ATP) channel inhibitor, fully reversed pinacidil-induced K(+) currents and partially reversed (∼58%) H(2)S-induced K(+) currents. Western blot analysis indicated that piglet arterioles expressed inwardly rectifying K(+) 6.1 (K(ir)6.1) channel and sulfonylurea receptor 2B (SUR2B) K(ATP) channel subunits. Pinacidil dilated pressurized (40 mmHg) piglet arterioles, and glibenclamide fully reversed this effect. Na(2)S also induced reversible and repeatable vasodilation with an EC(50) of ∼30 μM, and this effect was partially reversed (∼55%) by glibenclamide. Vasoregulation by H(2)S was also studied in pressurized resistance-size cerebral arteries of mice with a genetic deletion in the gene encoding SUR2 (SUR2 null). Pinacidil- and H(2)S-induced vasodilations were smaller in arterioles of SUR2 null mice than in wild-type controls. These data indicate that smooth muscle cell K(ATP) currents control newborn cerebral arteriole contractility and that H(2)S dilates cerebral arterioles by activating smooth muscle cell K(ATP) channels containing SUR2 subunits.
authors.affiliation: Dept. of Physiology, Univ. of Tennessee Health Science Ctr., Memphis, TN 38163, USA.
authors.forename: Guo Hua
authors.initials: GH
authors.lastname: Liang
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adebiyi
authors.forename: M Dennis
authors.initials: MD
authors.lastname: Leo
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: McNally
authors.forename: Charles W
authors.initials: CW
authors.lastname: Leffler
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Jaggar
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D011955:Receptors, Drug / Q000235:genetics / Q000378:metabolism; D064233:Sulfonylurea Receptors; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; C577511:Abcc9 protein, mouse; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014665:Vasodilator Agents; D020110:Pinacidil; D005905:Glyburide; D006862:Hydrogen Sulfide