期刊
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
卷 390, 期 4, 页码 397-408出版社
SPRINGER
DOI: 10.1007/s00210-016-1336-1
关键词
Nitroxyl; Nitric oxide; Diabetes; Endothelium-dependent relaxation; Vascular
资金
- Diabetes Australia Research Trust Grant [Y13G-KEMB]
- National Health & Medical Research Council (NHMRC) [546087]
Endothelial dysfunction is a major risk factor for the vascular complications of diabetes. Increased reactive oxygen species (ROS) generation, a hallmark of diabetes, reduces the bioavailability of endothelial vasodilators, including nitric oxide (NO center dot). The vascular endothelium also produces the one electron reduced and protonated form of NO center dot, nitroxyl (HNO). Unlike NO center dot, HNO is resistant to scavenging by superoxide anions (O-center dot(2)-). The fate of HNO in resistance arteries in diabetes is unknown. We tested the hypothesis that the vasodilator actions of endogenous and exogenous HNO are preserved in resistance arteries in diabetes. We investigated the actions of HNO in small arteries from the mesenteric and femoral beds as they exhibit marked differences in endothelial vasodilator function following 8 weeks of streptozotocin (STZ)-induced diabetes mellitus. Vascular reactivity was assessed using wire myography and O-center dot(2)- generation using lucigenin-enhanced chemiluminescence. The HNO donor, Angeli's salt, and the NO center dot donor, DEA/NO, evoked relaxations in both arteries of control rats, and these responses were unaffected by diabetes. Nox2 oxidase expression and O-center dot(2)- generation were upregulated in mesenteric, but unchanged, in femoral arteries of diabetic rats. Acetylcholine-induced endothelium-dependent relaxation was impaired in mesenteric but not femoral arteries in diabetes. The HNO scavenger, L-cysteine, reduced this endothelium-dependent relaxation to a similar extent in femoral and mesenteric arteries from control and diabetic animals. In conclusion, HNO and NO center dot contribute to the NO synthase (NOS)-sensitive component of endothelium-dependent relaxation in mesenteric and femoral arteries. The role of HNO is sustained in diabetes, serving to maintain endothelium-dependent relaxation.
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