Gender Differences in Aortic Endothelial Function in a Rat Model of Type 1 Diabetes: Possible Role of Super-oxide and Cyclooxygenase

Document Type

Conference Presentation

Conference Title/Conference Publication

American Physiological Sciences (APS) Conference

Location

Bloomfield, CO

Date of Presentation

7-17-2009

Abstract

To date little is known of the interaction between diabetes and sex hormones in the vasculature. The objectives of this study were to investigate whether there is a gender difference in the aortic endothelial function in streptozotocin (STZ, 65 mg/kg, iv)-induced diabetic rats, and the potential role of superoxide and cyclooxygenase (COX) metabolites in diabetes-induced vascular dysfunction. Endothelium dependent vasodilation (EDV) to acetylcholine (ACh; 10-8 to 10-5M) in aortic rings precontracted with phenylephrine (PE; 2µM) were obtained before and after pretreatment with MnTMPyP (10mM), a superoxide scavenger, or indomethacin (10µM), a COX inhibitor. Constrictor dose-response curves to PE (10-8 to 10-5M) were also generated before and after pretreatment with indomethacin. STZ-induced diabetes impaired EDV in both genders, but the effects of diabetes was more pronounced in females. Female diabetic rats also demonstrated a greater potentiation of the PE responses after indomethacin compared with males. Although, indomethacin reduced ACh-induced dilation in both male and female diabetic animals, prior incubation of rat aorta with MnTMPyP fully restored diabetes-induced impairment of EDV in both genders. These results suggest the predisposition of female rat aorta to vascular injury in diabetes, possibly via superoxide production. Furthermore, they suggest that COX metabolites play a role in the vascular reactivity of the aorta in diabetic rats (Supported by NIH/NIDCR).

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