Title

Gender differences in mesenteric endothelial function of streptozotocin-induced diabetic rats: Role of endothelium-derived relaxing factors

Document Type

Abstract

Publication Title

FASEB Journal

ISSN

0892-6638

Volume

25

Issue

Supp 1

DOI

10.1096/fasebj.25.1_supplement.631.5

Publication Date

1-1-2011

Abstract

Gender differences in mesenteric endothelial function were studied in male and female streptozotocin (60 mg/kg, iv)-induced diabetic rats. Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh, 10?8 to 10?5 M) in mesenteric arteries precontracted with phenylephrine (2 ?M) was measured before and after pretreatment with indomethacin (indo, 10 ?M), a cyclooxygenase inhibitor, L-NAME (200 ?M), a nitric oxide (NO) synthase inhibitor, or barium chloride (100 ?M), a Kir channel blocker, and ouabain (10 ?M), a Na+-K+-ATPase inhibitor. Significant impairment of EDV was observed only in diabetic females. Indo decreased the sensitivity to ACh only in control males. Addition of L-NAME reduced indo-resistant vasodilation in females, but its effect was much greater in diabetic females. In control males, however, L-NAME substantially blocked the remaining relaxation, and this effect was attenuated in diabetic males. Finally, the remaining indo- and L-NAME-resistant vasodilation was abolished by the combination of barium and ouabain in all groups. These data suggest that the predominant mediator in mesenteric vasodilation in females is endothelium-derived hyperpolarizing factors (EDHF), whereas in males it is NO. Furthermore, there was a shift in the contributions of EDHF to NO in females and NO to EDHF in males following the induction of diabetes (Supported by NIDCR).

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