title: Effect of type 1 diabetes on the production and vasoactivity of hydrogen sulfide in rat middle cerebral arteries.
abstract: Hydrogen sulfide (H2S) is produced endogenously in vascular tissue and has both vasoregulation and antioxidant effects. This study examines the effect of diabetes-induced oxidative stress on H2S production and function in rat middle cerebral arteries. Diabetes was induced in rats with streptozotocin (50 mg/kg, i.v.). Middle cerebral artery function was examined using a small vessel myograph and superoxide anion generation measured using nicotinamide adenine dinucleotide phosphate (NADPH)-dependent lucigenin-enhanced chemiluminescence. Cystathionine-γ-lyase (CSE) mRNA expression was measured via RT-PCR. Diabetic rats had elevated blood glucose and significantly reduced cerebral artery endothelial function. Maximum vasorelaxation to the H2S donor NaHS was unaffected in diabetic cerebral arteries and was elicited via a combination of K(+), Cl(-), and Ca(2+) channel modulation, although the contribution of Cl(-) channels was significantly less in the diabetic cerebral arteries. Vasorelaxation to the H2S precursor l-cysteine and CSE mRNA were significantly increased in diabetic cerebral arteries. Cerebral artery superoxide production was significantly increased in diabetes, but this increase was attenuated ex vivo by incubation with the H2S donor NaHS. These data confirm that cerebral artery endothelial dysfunction and oxidative stress occurs in diabetes. Endogenous H2S production and activity is upregulated in cerebral arteries in this model of diabetes. Vasorelaxation responses to exogenous H2S are preserved and exogenous H2S attenuates the enhanced cerebral artery generated superoxide observed in the diabetic group. These data suggest that upregulation of endogenous H2S in diabetes may play an antioxidant and vasoprotective role.
authors.affiliation: School of Medical Sciences and Health Innovations Research Institute, RMIT University Bundoora, Victoria, 3083, Australia.
authors.forename: Elosie Y
authors.initials: EY
authors.lastname: Streeter
authors.forename: Emilio
authors.initials: E
authors.lastname: Badoer
authors.forename: Owen L
authors.initials: OL
authors.lastname: Woodman
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Hart
keywords: Cerebral artery; diabetes; hydrogen sulfide; oxidative stress