Han Xiaoyuan, Shaligram Sonali, Zhang Rui, Anderson Leigh, Rahimian Roshanak
a Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, 3601 Pacific Ave., Stockton, CA 95211, USA.
b Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94115, USA.
Can J Physiol Pharmacol. 2016 Apr;94(4):408-15. doi: 10.1139/cjpp-2015-0272. Epub 2015 Sep 17.
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.
高血糖对男性和女性血管床的影响不同。我们之前已经表明，用链脲佐菌素（STZ）诱导糖尿病1周后，雄性和雌性大鼠的主动脉内皮功能存在差异。为了进一步研究这一现象，我们对糖尿病诱导8周（中期）后的雄性和雌性大鼠的主动脉反应进行了研究。在去氧肾上腺素（PE）预收缩的大鼠主动脉环中测量对乙酰胆碱（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处理前后生成对PE的浓度反应曲线。此外，还测定了内皮型一氧化氮合酶（eNOS）和NADPH氧化酶亚基（Nox1）的mRNA表达。在8周时，糖尿病对雌性主动脉EDV的损害程度大于雄性。此外，仅在雌性糖尿病大鼠中，对PE的反应性显著增强，并且如L-NAME处理后对PE反应的增强所示，雌性糖尿病大鼠主动脉中的基础NO降低至与雄性相同的水平。此外，糖尿病雌性大鼠中eNOS mRNA表达降低，而Nox1表达显著增强。这些结果表明，8周后雌性糖尿病大鼠的主动脉功能表现出更明显的损害，并且NO可能参与其中。
