OP15 Hydrogen sulfide protects endothelial function under conditions of oxidative stress

Abstract

Hydrogen sulfide is an endogenously produced gas that is reported to have anti-oxidant effects. The aim was to examine the capacity of the H2S donor, NaHS to scavenge superoxide anions (O2-) and to examine whether this effect elicited protection of endothelial function in oxidative stress. O2- were generated in Krebs’ solution via the reaction of hypoxanthine (Hx 100 μM) with xanthine oxidase (XO 0.01 U/ml) or pyrogallol (PG 20 μM). Thoracic aortae were collected from male C57Bl6/J mice and vascular reactivity and NO bioavailability were examined by myography. NaHS scavenged O2- generated from Hx–XO in Krebs’ solution in a concentration-dependent manner (maximum reduction 59 ± 4%, IC50 0.12 μM, P < 0.001). Aortic rings exposed to either Hx–XO or PG in the myograph displayed significantly attenuated vasorelaxation to the endothelium-dependent vasodilator acetylcholine (control: 90 ± 7%, Hx–XO: 58 ± 4%, PG: 65.3 ± 4.0%, P < 0.001) which was completely reversed by NaHS (100 μM) or superoxide dismutase (250 U/ml). Similarly, NO bioavailability was attenuated by PG (P < 0.05), but restored by NaHS (100 μM). NaHS treatment (100–100 μM) for 30 min inhibited vascular O2- generation in a concentration-dependent manner (maximum reduction 88 ± 3%, IC50 2.4 μM, P < 0.001). This effect persisted when the aortic segments were incubated with NaHS (100–100 μM) for 30 min and the NaHS washed out before NADPH (100 μM) was added (maximum reduction 58 + 7%, IC50 0.4 μM, P < 0.001).