Izmir Katip Celebi University Faculty of Medicine, Department of Pharmacology Izmir, Turkey.
University of Health Sciences Tepecik Training and Research Hospital Department of Obstetrics and Gynecology Izmir, Turkey.
Eur J Obstet Gynecol Reprod Biol. 2023 Jan;280:168-173. doi: 10.1016/j.ejogrb.2022.12.009. Epub 2022 Dec 9.
Potassium (K) channel openers and calcium (Ca) channel blockers are currently used to treat acute severe hypertension in pregnancy. We aimed to investigate the vasorelaxant effect of NS11021, a potent and specific big-conductance Ca-activated K (BKCa) channel activator, and to compare it with the vasorelaxant effect of nifedipine on human umbilical arteries (HUAs) isolated from healthy and preeclamptic pregnants.
A total of 29 HUAs were isolated immediately after delivery from 14 healthy and 15 preeclamptic pregnant with severe features. The concentration-dependent relaxation responses were obtained to nifedipine and NS11021 on HUAs precontracted with endothelin-1 (ET-1) (10 M) in an isolated tissue bath.
Both nifedipine and NS11021 caused concentration-dependent relaxation responses in HUAs from healthy and preeclamptic pregnants. While the maximum responses (Emax) and pD values of nifedipine did not change significantly in both groups, the Emax and pD values of NS11021 were significantly decreased in the preeclampsia group (Emax ± SEM; %75.57 ± 4.53 and %43.75 ± 14.00 and pD ± SEM; 6.92 ± 0.26 and 5.24 ± 0.53 respectively, p < 0.05). In addition, the pD value of NS11021 was not significantly different from that of nifedipine in the control group, but decreased significantly in the preeclampsia group (pD ± SEM 7.1 ± 0.41 and 5.2 ± 0.53, p < 0.05, respectively).
Efficacy and potency of NS11021 decreased in HUAs from preeclamptic pregnants. Also, NS11021 is less potent than nifedipine in the preeclampsia group. BKCa channels may have a role in the pathogenesis of preeclampsia, however, further experimental studies are needed to elucidate that.
钾(K)通道开放剂和钙(Ca)通道阻滞剂目前用于治疗妊娠急性重度高血压。我们旨在研究 NS11021 的血管舒张作用,NS11021 是一种有效的、特异性的大电导钙激活钾(BKCa)通道激活剂,并将其与硝苯地平对来自健康和子痫前期孕妇的人脐动脉(HUA)的血管舒张作用进行比较。
总共从 14 名健康和 15 名严重特征子痫前期孕妇分娩后立即分离了 29 个 HUA。在离体组织浴中,用内皮素-1(ET-1)(10μM)预收缩 HUA,测定硝苯地平和 NS11021 对 HUAs 的浓度依赖性舒张反应。
硝苯地平和 NS11021 均导致健康和子痫前期孕妇的 HUAs 产生浓度依赖性舒张反应。虽然硝苯地平在两组中的最大反应(Emax)和 pD 值没有显著变化,但 NS11021 在子痫前期组中的 Emax 和 pD 值显著降低(Emax±SEM;%75.57±4.53 和%43.75±14.00 和 pD±SEM;6.92±0.26 和 5.24±0.53,p<0.05)。此外,NS11021 的 pD 值在对照组中与硝苯地平无显著差异,但在子痫前期组中显著降低(pD±SEM 7.1±0.41 和 5.2±0.53,p<0.05)。
NS11021 在子痫前期孕妇的 HUA 中的疗效和效力降低。此外,NS11021 在子痫前期组中的效力低于硝苯地平。BKCa 通道可能在子痫前期的发病机制中起作用,但需要进一步的实验研究来阐明这一点。