Vascular Mechanisms in Pregnancy-Induced Hypertension

描述（由申请人提供）：正常妊娠与 全身血管阻力降低，肾血流量增加， 降低动脉压。在5%到10%的怀孕中， 一种称为先兆子痫的疾病，其特征是蛋白尿，全身性增加， 肾血管阻力与妊娠高血压综合征（PIH）; 然而，这种疾病的潜在机制尚未清楚 鉴定子宫胎盘灌注减少， 妊娠晚期的局部缺血被认为是引发 体循环血管阻力和妊高征;然而，中间血管和 涉及的细胞机制尚不清楚。本报告的总体目标 建议是测试中心假设，局部减少， 妊娠晚期子宫胎盘灌注与全身性 内皮依赖性血管舒张的减少和血管舒张的增加 平滑肌反应性导致全身血管收缩，增加 血管阻力和高血压。血管舒张功能下降 由于一氧化氮-cGMP和/或前列环素-cAMP的抑制 弛豫途径血管平滑肌反应性增加是由于 血管平滑肌对血管收缩剂敏感性增加的结果 导致增加

DESCRIPTION (provided by the applicant): Normal pregnancy is associated with reduction in systemic vascular resistance, increased renal blood flow and decreased arterial pressure. In 5 to 10 percent of pregnancies, women develop a condition called preeclampsia characterized-by proteinuria, increased systemic and renal vascular resistance and pregnancy-induced hypertension (PIH); however, the mechanisms underlying this disorder have not yet been clearly identified. Reduction in uteroplacental perfusion and the ensuing placental ischemia during late pregnancy have been proposed to trigger the increases in systemic vascular resistance and PIH; however, the intermediary vascular and cellular mechanisms involved are unclear. The overall objective of this proposal is to test the central hypothesis that localized reduction in uteroplacental perfusion during late pregnancy is associated with generalized decrease in endothelium-dependent vascular relaxation and increase in vascular smooth muscle reactivity leading to generalized vasoconstriction, increased vascular resistance and hypertension. The decreased vascular relaxation occurs as a result of inhibition of the nitric oxide-cGMP and/or the prostacyclin-cAMP relaxation pathway. The increased vascular smooth muscle reactivity occurs as a result of increased sensitivity of vascular smooth muscle to vasoconstrictors leading to increased