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Role of Oxidative Stress in Arterial Dysfunction in Type 2 Diabetes Mellitus
Author(s) -
RodriguezAlvarez Walter E.,
Lawal Rasheed,
Harris Clarissa,
Williams Brianna,
Adeagbo ASO,
Joshua Irving G.,
Tyagi Suresh C.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.641.4
Oxidative stress (OS) in Type 2 Diabetes (T2D) impairs vascular function by decreasing nitric oxide (NO) bioavailability; and contributes to arterial stiffness by increasing MMP activity. We hypothesized that homocysteine (Hcy) decreases NO availability and impairs endothelial dependent relaxation by increasing OS, and antioxidant treatment with Tempol (T) and folic acid (FA) will attenuate this effect. Vascular function and levels of MMP and TIMP were determined in thoracic aorta segments of male C57BL/6J mice (n=8/group) fed a High Cal‐Diet (HCD) for 6 weeks. Mice were grouped into HCD, HCD+T, HCD+FA, Low Cal‐ Diet (LCD), LCD+T, and LCD+FA mice. Acetylcholine‐induced relaxation response of the aortic rings was decreased by 50% in HCD as compared to LCD group, but normalized up to 80% in HCD+T and HCD+FA groups. The contraction response to phenylephrine was decreased by 30% in HCD as compared to LCD, but normalized in T2D+FA and in T2D+T groups. Levels of MMPs were higher in aortic tissue from HCD as compared to the LCD group, and were reduced in T2D+FA and in T2D+T groups. Levels of TIMPs were lower in aortic tissue from HCD as compared to the LCD, and were normalized in T2D+FA and in T2D+T groups. Our results suggested that the attenuation of vascular dysfunction in T2D mice by FA and T is associated with decreased MMP levels in vascular tissue. Supported by grants from NIH‐NHLBI