3′,4′-Dihydroxyflavonol restores endothelium-dependent relaxation in small mesenteric artery from rats with type 1 and type 2 diabetes

• Published in: European journal of pharmacology 2011-06, Vol.659 (2), p.193-198
• Main Authors: Leo, Chen-Huei, Hart, Joanne L., Woodman, Owen L.
• Format: Article
• Language: English
• Subjects: 3′,4′-Dihydroxyflavonol; acetylcholine; Animals; Antioxidant; antioxidant activity; antioxidants; Antioxidants - metabolism; Biological and medical sciences; Biomimetic Materials - pharmacology; Blood Glucose - metabolism; Body Weight - drug effects; chemiluminescence; Cyclic N-Oxides - pharmacology; Diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelial function; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; flavonols; Flavonols - pharmacology; Medical sciences; mesenteric arteries; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiopathology; Metalloporphyrins - pharmacology; Microvessels - drug effects; Microvessels - physiopathology; noninsulin-dependent diabetes mellitus; oxidants; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley - metabolism; reactive oxygen species; Spin Labels; Superoxide; superoxide dismutase; Superoxides - metabolism; Vasodilation - drug effects
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2011.03.018

Diabetes is known to cause an overproduction of reactive oxygen species (ROS), contributing to the impairment of endothelium-dependent relaxation in microvasculature, however it is not clear whether antioxidants are able to reverse microvascular endothelial dysfunction. The aim of this study is to investigate whether the synthetic flavonol 3′,4′-dihydroxyflavonol (DiOHF) could reduce the levels of reactive oxygen species (ROS) and improve endothelium-dependent relaxation in mesenteric arteries from both type 1 and type 2 diabetic rats. Endothelial function of third order mesenteric arteries from type 1 and type 2 diabetic rats was assessed using wire-myography. Superoxide levels in the mesenteric arteries were measured by L-012-induced chemiluminescence. Mesenteric arteries from type 1 and type 2 diabetic rats had elevated levels of superoxide production compared to control, which was accompanied by impaired responses to the endothelium-dependent relaxant, acetylcholine (ACh). The acute presence of DiOHF ex vivo significantly reduced the superoxide levels in the diabetic mesenteric arteries and restored endothelial function. The antioxidant activity of DiOHF is comparable to superoxide dismutase mimetics (tempol and MnTMPyP), which also significantly reduced the superoxide levels and improved endothelial function in diabetic arteries. Therefore, the synthetic flavonol DiOHF could effectively reduce oxidant stress and restore microvascular endothelium-dependent relaxation in diabetic rats.