Pharmacology, University of Nevada, Reno School of Medicine, Reno, Nevada.
J Cell Mol Med. 2018 Dec;22(12):6391-6395. doi: 10.1111/jcmm.13883. Epub 2018 Sep 6.
Preterm birth before 37 weeks of completed gestation results in numerous health consequences for the foetus. Preterm labour leads to preterm birth in over 50% of cases, and no FDA-approved treatment can prevent labour or help a foetus remain in the womb until term. Examination of nitric oxide mediated relaxation signaling in the uterine smooth muscle reveals a role for protein S-nitrosation. The recent discovery of upregulated S-nitrosoglutathione reductase (GSNOR) in spontaneously preterm labouring women has emphasized the need to explore the function of S-nitrosation regulation in the maintenance of uterine quiescence. Here we have examined the ability of nebivolol to relax uterine smooth muscle and tested recent claims that nebivolol is a GSNOR inhibitor. In uterine smooth muscle strips from both mouse and human, nebivolol relaxes oxytocin-induced contractions in a dose dependent manner. Our data indicates that nebivolol has no effect on GSNOR activity, nor does nebivolol inhibit thioredoxin reductase, two of the major protein denitrosylases. The ability of nebivolol to relax uterine smooth muscle is likely the combined effects of increased nitric oxide synthase activity and β3-adregnegic stimulation.
早产发生于妊娠 37 周前，会导致胎儿出现许多健康问题。超过 50%的早产是由于早产宫缩引起的，目前没有获得 FDA 批准的治疗方法可以预防宫缩或帮助胎儿在子宫内维持到足月。对一氧化氮介导的子宫平滑肌松弛信号的研究揭示了蛋白质 S-亚硝基化的作用。最近在自发性早产的妇女中发现上调的 S-亚硝基谷胱甘肽还原酶（GSNOR），强调了需要探索 S-亚硝基化调节在维持子宫静止中的功能。在这里，我们检查了尼群地平松弛子宫平滑肌的能力，并测试了尼群地平是 GSNOR 抑制剂的最新说法。在来自小鼠和人的子宫平滑肌条带中，尼群地平以剂量依赖的方式松弛催产素诱导的收缩。我们的数据表明，尼群地平对 GSNOR 活性没有影响，也不抑制硫氧还蛋白还原酶，这两种主要的蛋白质去亚硝基酶。尼群地平松弛子宫平滑肌的能力可能是一氧化氮合酶活性增加和β3-肾上腺素能刺激的综合作用。
