Sex-based Differences in the Aortic Function of UCD-T2DM Rats: A Novel Rat Model of Type 2 Diabetes Mellitus

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UC Davis type 2 diabetes mellitus (UCD-T2DM) Rat is a validated model of type 2 diabetes mellitus. UCD-T2DM rats are characterized by polygenic, adult-onset obesity and spontaneous β-cell failure and, as a result, more closely models the pathophysiology of type 2 diabetes in humans than other rodent models of the disease. The objective of this study was to investigate alterations in aortic endothelial function in the UCD-T2DM Rat model and to determine whether there is a sexual dimorphism in diabetes-induced aortic dysfunction. Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh, 10−8 to 10−5M) was measured in intact aortic rings pre-contracted with phenylephrine (PE, 2μM). Endothelium-independent vasodilation to sodium nitroprusside (SNP, 10−9 to 10−5 M) was assessed in endothelium-denuded rings pre-contracted with PE (2μM). Furthermore, constrictor response curves to PE (10−8 to 10−5 M) were generated. Diabetes significantly impaired relaxation responses to ACh and SNP in aortic rings from female UCD-T2DM Rats, however, potentiated the relaxation in males. Moreover, diabetes significantly shifted PE contractile responses to the left in aortic rings of both sexes. Both maximal contraction and sensitivity to PE in aortic rings from diabetic females were significantly higher than those in control rats. In males, diabetes did not affect the maximal contraction to PE. These data, for the first time, show that the vascular function in aortic rings of UCD-T2DM is altered in both sexes. The decreased sensitivity of vascular smooth muscle to NO along with the enhanced contractile responsiveness to PE may in part contribute to the attenuated relaxation response to ACh in diabetic female rats. On the other hand, an elevated sensitivity of vascular smooth muscle to NO may partially explain the potentiation of ACh responses in diabetic males. The overall results indicate the presence of sex-based differences in the aortic function of UCD-T2DM Rats. This abstract is from the Experimental Biology 2016 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.