Ghulmiyyah Labib M, Tamayo Esther, Clark Shannon M, Hankins Gary D V, Anderson Garland D, Saade George R, Longo Monica
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555-0144, USA.
Am J Obstet Gynecol. 2007 Sep;197(3):279.e1-5. doi: 10.1016/j.ajog.2007.06.062.
Nitric oxide deficiency has been implicated in adverse pregnancy outcomes. Mice that lack endothelial nitric oxide synthase (NOS3) have abnormal in vitro vascular reactivity. Our objective was to assess the effect of a previous pregnancy on the abnormal vascular function of NOS3 knockout mice.
Carotid arteries from pregnant NOS3 knockout (NOS3(-/-KO)) and wild-type control mice (NOS3(+/+WT)) from first and second pregnancy were obtained for in vitro vascular reactivity studies. Vascular responses to cumulative concentrations of the vasoconstrictors phenylephrine, serotonin, and thromboxane and the vasorelaxants acetylcholine, sodium nitroprusside, and isoproterenol were determined.
In the first pregnancy, contractile responses were exaggerated in the knockout animals, compared with the wild-type animals. However, the second pregnancy in knockout animals was associated with normalization of responses to phenylephrine and serotonin and increased responses to the endothelium-independent relaxants.
The vascular function of NOS3 knockout mice improves with subsequent pregnancy becoming comparable to wild-type animals.
一氧化氮缺乏与不良妊娠结局有关。缺乏内皮型一氧化氮合酶（NOS3）的小鼠具有异常的体外血管反应性。我们的目的是评估既往妊娠对NOS3基因敲除小鼠异常血管功能的影响。
获取首次妊娠和第二次妊娠的妊娠NOS3基因敲除（NOS3(-/-KO)）小鼠和野生型对照小鼠（NOS3(+/+WT)）的颈动脉，进行体外血管反应性研究。测定血管对累积浓度的血管收缩剂去氧肾上腺素、5-羟色胺和血栓素以及血管舒张剂乙酰胆碱、硝普钠和异丙肾上腺素的反应。
在首次妊娠中，与野生型动物相比，基因敲除动物的收缩反应增强。然而，基因敲除动物的第二次妊娠与对去氧肾上腺素和5-羟色胺反应的正常化以及对内皮依赖性舒张剂反应的增加有关。
NOS3基因敲除小鼠的血管功能随着后续妊娠而改善，变得与野生型动物相当。
