Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
Basic Clin Pharmacol Toxicol. 2020 Aug;127(2):152-159. doi: 10.1111/bcpt.13413. Epub 2020 May 4.
We investigated whether sex differences exist in cyclooxygenase-dependent effects on membrane potential and relaxation in mice mesenteric resistance arteries. Mesenteric small arteries of 9- to 12-week-old, male and female, wild-type mice, db/+ mice and diabetic db/db mice were mounted in myographs for measurements of isobaric diameter and smooth muscle cell membrane potential. Acetylcholine caused smaller dilation of arteries from male db/+ mice compared to arteries from female db/+ mice. In the presence of the NO synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME), acetylcholine-induced dilation of arteries from males increased in the presence of indomethacin and the COX-1-specific inhibitor FR122047. The presence of indomethacin was also associated with a more negative membrane potential in arteries from males. In arteries from db/db mice, no sex differences were seen. In arteries from male but not female wild-type mice, the thromboxane receptor blocker SQ29,548 increased relaxation to acetylcholine. In contrast to arteries from female mice, COX (most likely COX-1)-derived prostanoids and activation of thromboxane receptors counteract acetylcholine vasodilatation probably through increased smooth muscle depolarization in arteries from male mice. In mice with diabetes and pronounced endothelial dysfunction, inhibition of COX did not enhance acetylcholine vasodilatation.
我们研究了环氧化酶依赖性对雄性和雌性小鼠肠系膜阻力动脉膜电位和松弛的影响是否存在性别差异。将 9-12 周龄雄性和雌性野生型小鼠、db/+ 小鼠和糖尿病 db/db 小鼠的肠系膜小动脉安装在肌动描记器上，以测量等压直径和平滑肌细胞膜电位。与雌性 db/+ 小鼠的动脉相比，乙酰胆碱引起雄性 db/+ 小鼠的动脉扩张幅度较小。在存在一氧化氮合酶抑制剂 N-硝基-L-精氨酸甲酯 (L-NAME) 的情况下，在存在吲哚美辛和 COX-1 特异性抑制剂 FR122047 的情况下，雄性小鼠的动脉中乙酰胆碱诱导的扩张增加。吲哚美辛的存在也与雄性动脉的膜电位更负有关。在 db/db 小鼠的动脉中，没有观察到性别差异。在雄性而非雌性野生型小鼠的动脉中，血栓素受体阻滞剂 SQ29,548 增加了对乙酰胆碱的松弛反应。与雌性小鼠的动脉不同，COX（很可能是 COX-1）衍生的前列腺素和血栓素受体的激活可能通过增加雄性小鼠动脉的平滑肌去极化来对抗乙酰胆碱的血管舒张作用。在糖尿病和明显内皮功能障碍的小鼠中，COX 抑制并未增强乙酰胆碱的血管舒张作用。
