Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA.
Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, Stockton, CA 94115, USA.
Int J Mol Sci. 2024 Oct 21;25(20):11328. doi: 10.3390/ijms252011328.
Several reports, including our previous studies, indicate that hyperglycemia and diabetes mellitus exert differential effects on vascular function in males and females. This study examines sex differences in the vascular effects of type 2 diabetes (T2D) in an established monogenic model of obesity-induced T2D, Zucker Diabetic Fatty (ZDF) rats. Acetylcholine (ACh) responses were assessed in phenylephrine pre-contracted rings before and after apocynin, a NADPH oxidase (NOX) inhibitor. The mRNA expressions of aortic endothelial NOS (eNOS), and key NOX isoforms were also measured. We demonstrated the following: (1) diabetes had contrasting effects on aortic vasorelaxation in ZDF rats, impairing relaxation to ACh in females while enhancing it in male ZDF rats; (2) inhibition of NOX, a major source of superoxide in vasculature, restored aortic vasorelaxation in female ZDF rats; and (3) eNOS and NOX4 mRNA expressions were elevated in female (but not male) ZDF rat aortas compared to their respective leans. This study highlights sexual dimorphism in ACh-mediated vasorelaxation in the aorta of ZDF rats, suggesting that superoxide may play a role in the impaired vasorelaxation observed in female ZDF rats.
包括我们之前的研究在内的几项报告表明，高血糖和糖尿病对男性和女性的血管功能有不同的影响。本研究在肥胖诱导的 2 型糖尿病（T2D）的一种既定单基因模型—— Zucker 糖尿病肥胖（ZDF）大鼠中，检查了 T2D 的血管效应中的性别差异。在预先用苯肾上腺素收缩的环中评估了乙酰胆碱（ACh）的反应，然后用 NADPH 氧化酶（NOX）抑制剂 apocynin 进行处理。还测量了主动脉内皮型一氧化氮合酶（eNOS）和关键的 NOX 同工型的 mRNA 表达。我们证明了以下几点：（1）糖尿病对 ZDF 大鼠的主动脉血管舒张有相反的影响，在雌性中损害 ACh 引起的舒张，而在雄性 ZDF 大鼠中增强；（2）抑制 NOX，一种血管中超氧化物的主要来源，恢复了雌性 ZDF 大鼠的主动脉血管舒张；（3）与各自的 lean 相比，eNOS 和 NOX4 的 mRNA 表达在雌性（但不是雄性）ZDF 大鼠的主动脉中升高。本研究强调了 ZDF 大鼠主动脉中 ACh 介导的血管舒张的性别二态性，表明超氧化物可能在雌性 ZDF 大鼠中观察到的血管舒张受损中起作用。
