Sexual dimorphism in mesenteric arterial function of a novel rat model of type 2 diabetes, UC Davis-Type 2 Diabetes Mellitus (UCD-T2DM)

Document Type

Abstract

Publication Title

FASEB Journal

ISSN

0892-6638

Volume

30

Issue

Supp 1

DOI

10.1096/fasebj.30.1_supplement.738.7

Publication Date

4-1-2016

Abstract

This is the first study to characterize the vascular functions in a well characterized and validated polygenic rat model of type 2 diabetes (UC Davis-Type 2 Diabetes Mellitus, UCD-T2DM), exhibiting etiology more similar to clinical T2DM in humans than other rodent models. The objectives of this study were to investigate whether 1) the endothelium-dependent and -independent vasodilation in mesenteric arteries (MA) are impaired, 2) sex differences exist in the development of abnormal vascular responses, and 3) the relative contributions of endothelium derived relaxing factors in modulating vascular reactivity of MA is altered in UCD-T2DM Rats. Endothelium-dependent vasodilation to acetylcholine (ACh, 10−8 to 10−5 M) in pre-contracted arteries with phenylephrine (PE, 2 μM) was measured before and after pre-treatment with indomethacin (cyclooxygenase inhibitor, 10 μM), L-NAME (nitric oxide synthase inhibitor, 200 μM), or barium chloride (KIR blocker, 100 μM) plus ouabain (Na+-K+-ATPase inhibitor, 10 μM). Vascular responses to sodium nitroprusside (SNP) (endothelium-independent vasodilator, 10−9 to 10−5 M) and contractile agents such as PE (10−7 to 3×10−5 M) or endothelin-1 (ET-1, 10−10 to 10−7 M) were also determined. Both ACh- and SNP-induced relaxation were significantly impaired in MA of diabetic rats, regardless of sex. However, the extent of impairment was greater in female diabetic rats compared to male diabetic animals. Diabetes also significantly increased sensitivity to PE or ET-1 in females compared to males. Finally, the relative importance of endothelium-derived hyperpolarizing factor (EDHF) to vascular regulation was lost in diabetic rats, regardless of sex. These data, for the first time, show that the endothelial function in MA of UCD-T2DM Rats is impaired in both sexes, possibly due to the loss of EDHF, initially a major vasodilatory factor. Furthermore, we showed a greater predisposition of MA to injury in diabetic female rats, in part due to a higher sensitivity of female arteries to contractile agents. This abstract is from the Experimental Biology 2016 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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