Vascular Mechanisms in Pregnancy-Induced Hypertension

描述(申请人提供)：正常妊娠与 降低全身血管阻力，增加肾脏血流量和 动脉压下降。在5%到10%的怀孕中，女性会患上 一种称为子痫前期的疾病--以蛋白尿为特征，全身性增加 肾血管阻力与妊娠高血压综合征(PIH)； 然而，导致这种疾病的机制尚不清楚。 已确认身份。子宫胎盘灌注量的减少及随之而来的胎盘 妊娠晚期的缺血被认为是导致血管紧张素转换酶活性增加的原因 体循环血管阻力与妊高征；然而，中间血管和 其中涉及的细胞机制尚不清楚。这样做的总体目标是 建议是检验中心假设，即局部减排 妊娠晚期子宫胎盘灌注与全身性 内皮依赖性血管舒张性降低和血管紧张性增加 导致全身性血管收缩的平滑肌反应性增加 血管阻力和高血压。血管松弛程度降低 由于抑制一氧化氮-cGMP和/或前列环素-cAMP 松弛通路。血管平滑肌反应性的增加发生在 血管平滑肌对血管收缩药敏感性增加的结果 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