Rosenfeld Charles R, Roy Tim, DeSpain Kevin, Cox Blair E
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, UT Southwestern Medical Center at Dallas, USA.
J Soc Gynecol Investig. 2005 Sep;12(6):402-8. doi: 10.1016/j.jsgi.2005.04.009.
The mechanisms regulating basal uteroplacental blood flow (UBF) and the greater than 30-fold increase observed in normal pregnancy remain unclear. Although vascular growth contributes in early gestation, vasodilation accounts for the exponential rise seen in the last third of pregnancy. Large conductance potassium channels (BK(Ca)) are expressed in uterine vascular smooth muscle (VSM), but the extent of their role in regulating UBF in pregnancy is unclear. Therefore, we determined if BK(Ca) regulate basal UBF during ovine pregnancy.
Studies were performed at 113 to 127 days and 135 to 150 days of gestation in eight pregnant ewes instrumented with uterine artery flow probes and uterine arterial and venous catheters. Tetraethylammonium chloride (TEA), a BK(Ca)-specific inhibitor at less than 1.0 mM, was infused intra-arterially into the pregnant uterine horn over 60 minutes to achieve levels of 0.001-0.35 mM while continuously monitoring UBF, arterial pressure (MAP), and heart rate (HR). Uterine arterial and venous blood was collected simultaneously to measure uterine cyclic guanosine monophosphate (cGMP) synthesis.
Intra-arterial TEA dose-dependently decreased basal UBF in the early (R = 0.81, n = 36, P <.001) and late (R = 0.72, n = 31, P <.001) study periods without altering contralateral UBF, MAP, and HR. The IC(50) was 0.2 mM and basal UBF decreased >or=80% at 0.35 mM in both periods. Although UBF fell greater than 40% at estimated plasma TEA levels of 0.3 mM, uterine arterial cGMP was unchanged, uterine venous cGMP rose, and uterine cGMP synthesis was unchanged; therefore, upstream events associated with BK(Ca) activation were unaffected by blockade.
These are the first data demonstrating that BK(Ca) are essential in the maintenance of basal UBF in the last third of ovine pregnancy.
调节基础子宫胎盘血流量（UBF）的机制以及正常妊娠期间观察到的超过30倍的增加仍不清楚。虽然血管生长在妊娠早期起作用，但血管舒张是妊娠最后三分之一期出现指数级上升的原因。大电导钾通道（BK（Ca））在子宫血管平滑肌（VSM）中表达，但其在调节妊娠期间UBF中的作用程度尚不清楚。因此，我们确定BK（Ca）是否在绵羊妊娠期间调节基础UBF。
在113至127天和135至150天的妊娠期对8只怀孕母羊进行研究，这些母羊配备了子宫动脉血流探头以及子宫动脉和静脉导管。在60分钟内将小于1.0 mM的BK（Ca）特异性抑制剂氯化四乙铵（TEA）动脉内注入怀孕的子宫角，以达到0.001 - 0.35 mM的水平，同时持续监测UBF、动脉压（MAP）和心率（HR）。同时采集子宫动脉和静脉血以测量子宫环磷酸鸟苷（cGMP）合成。
在早期（R = 0.81，n = 36，P <.001）和晚期（R = 0.72，n = 31，P <.001）研究期间，动脉内注入TEA剂量依赖性地降低基础UBF，而不改变对侧UBF、MAP和HR。半数抑制浓度（IC50）为0.2 mM，在两个时期0.35 mM时基础UBF降低≥80%。虽然在估计血浆TEA水平为0.3 mM时UBF下降超过40%，但子宫动脉cGMP未改变，子宫静脉cGMP升高，子宫cGMP合成未改变；因此，与BK（Ca）激活相关的上游事件不受阻断影响。
这些是首批数据，表明BK（Ca）对维持绵羊妊娠最后三分之一期的基础UBF至关重要。
