The potentiation of EDV in diabetic male aortas was accompanied by a traces of nitric oxide (NO)- and prostanoid-independent relaxation and elevated aortic expression of small- and intermediate conductance Ca 2+-activated K + channels in this group. Diabetes slightly but significantly impaired EDV in response to ACh in aortas from females but potentiated the relaxation response in males. Metabolic parameters and expression of molecules associated with vascular and insulin signaling as well as reactive oxygen species generation were determined. Moreover, contractile responses to phenylephrine (PE) were measured before and after incubation of aortic rings with a nitric oxide synthase (NOS) inhibitor in the presence of indomethacin. Relaxation responses to sodium nitroprusside were assessed in endothelium-denuded rings. Endothelium-dependent vasorelaxation (EDV) in response to acetylcholine (ACh) was measured in aortic rings before and after exposure to pharmacological inhibitors. The objectives of this study were to examine whether there were (1) sex differences in aortic function and (2) alterations in the relative contribution of endothelium-derived relaxing factors in modulating aortic reactivity in UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rats. Previous reports suggest that diabetes may differentially affect the vascular beds of females and males.

4Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, United States.

3Department of Nutrition, University of California, Davis, Davis, CA, United States.

2Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.

Long School of Pharmacy, University of the Pacific, Stockton, CA, United States 1Department of Physiology & Pharmacology, Thomas J.Allen 4, José Pablo Vázquez-Medina 4, Peter J. Farjana Akther 1, Md Rahatullah Razan 1, Sonali Shaligram 1, James L.

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