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Sex-specific vascular responses of the rat aorta: effects of moderate term (intermediate stage) streptozotocin-induced diabetes

机译:大鼠主动脉的性别特异性血管反应:链脲佐菌素诱发的糖尿病(中期)的影响

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摘要

Hyperglycemia affects male and female vascular beds differently. We have previously shown that 1 week after the induction of diabetes with streptozotocin (STZ), male and female rats exhibit differences in aortic endothelial function. To examine this phenomenon further, aortic responses were studied in male and female rats 8 weeks after the induction of diabetes (intermediate stage). Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh) was measured in phenylephrine (PE) pre-contracted rat aortic rings. Concentration response curves to PE were generated before and after L-NAME, a nitric oxide synthase (NOS) inhibitor. Furthermore, mRNA expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase subunit (Nox1) were determined. At 8 weeks, diabetes impaired EDV to a greater extent in female than male aortae. Furthermore, the responsiveness to PE was significantly enhanced only in female diabetic rats, and basal NO, as indicated by the potentiation of the response to PE after L-NAME, was reduced in female diabetic rat aortae to the same levels as in males. In addition, eNOS mRNA expression was decreased, while the Nox1 expression was significantly enhanced in diabetic female rats. These results suggest that aortic function in female diabetic rats after 8 weeks exhibits a more prominent impairment and that NO may be involved.
机译:高血糖对男性和女性血管床的影响不同。先前我们已经表明,链脲佐菌素(STZ)诱导糖尿病1周后,雄性和雌性大鼠在主动脉内皮功能上均表现出差异。为了进一步检查该现象,在雄性和雌性大鼠诱导糖尿病后8周(中期)研究了主动脉反应。在去氧肾上腺素(PE)预收缩的大鼠主动脉环中测量了对乙酰胆碱(ACh)的内皮依赖性血管舒张(EDV)。在一氧化氮合酶(NOS)抑制剂L-NAME之前和之后,生成对PE的浓度响应曲线。此外,测定了内皮一氧化氮合酶(eNOS)和NADPH氧化酶亚基(Nox1)的mRNA表达。在8周时,女性比男性主动脉更严重地损害了EDV。此外,仅在雌性糖尿病大鼠中对PE的应答性显着增强,并且如在L-NAME后对PE的应答增强所表明的,基础NO在雌性糖尿病大鼠主动脉中降低至与雄性相同的水平。此外,在糖尿病雌性大鼠中,eNOS mRNA表达降低,而Nox1表达显着增强。这些结果表明,雌性糖尿病大鼠的主动脉功能在8周后表现出更明显的损伤,并且可能涉及NO。

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