Mechanisms of enhanced vascular reactivity in preeclampsia.
Mechanisms of enhanced vascular reactivity in preeclampsia.
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DOI：
10.1161/hypertensionaha.111.176602
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发表时间：
2011-11
期刊：
影响因子：
--
通讯作者：
Walsh SW
中科院分区：
文献类型：
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作者：
Mishra N;Nugent WH;Mahavadi S;Walsh SW
先兆子痫妇女对血管紧张素II的血压反应增强，全身血管广泛浸润中性粒细胞。中性粒细胞释放活性氧，可能激活RhoA激酶途径，以增强血管反应性。我们假设先兆子痫患者血管反应性增强是由于中性粒细胞介导的活性氧类激活RhoA激酶途径所致。在剖腹产时获得网膜动脉，并使用肌描记系统进行研究。我们发现先兆子痫妇女的动脉有广泛的中性粒细胞浸润和对血管紧张素II的反应性增强。用活性氧或活化的中性粒细胞治疗正常孕妇的动脉，增强血管对血管紧张素II的反应性，模拟先兆子痫血管。用超氧化物歧化酶/过氧化氢酶预处理以淬灭活性氧，或RhoA激酶抑制剂阻断先兆子痫和正常血管中增强的反应。活性氧也增强血管对去甲肾上腺素的反应性，这被RhoA激酶抑制所阻断。用活性氧处理动脉使RhoA激酶活性增加3倍，而用血管紧张素II和活化的中性粒细胞或活性氧培养人血管平滑肌细胞导致RhoA激酶途径中关键蛋白的磷酸化。我们的结论是，增强血管反应性的网膜动脉先兆子痫是由于活性氧激活的RhoA激酶途径，增强血管反应性可能是由于中性粒细胞的浸润。我们推测，中性粒细胞浸润到系统血管的先兆子痫妇女是一个重要的机制，高血压。
Preeclamptic women have enhanced blood pressure response to angiotensin II and extensive systemic vascular infiltration of neutrophils. Neutrophils release reactive oxygen species that might activate the RhoA kinase pathway to enhance vascular reactivity. We hypothesized that enhanced vascular reactivity in preeclampsia is due to neutrophil mediated reactive oxygen species activation of the RhoA kinase pathway. Omental arteries were obtained at cesarean section and studied using a myograph system. We found that arteries of preeclamptic women had extensive infiltration of neutrophils and enhanced reactivity to angiotensin II. Treatment of arteries of normal pregnant women with reactive oxygen species or activated neutrophils enhanced vessel reactivity to angiotensin II mimicking preeclamptic vessels. Pretreatment with superoxide dismutase/catalase to quench reactive oxygen species, or RhoA kinase inhibitor blocked enhanced responses in preeclamptic and normal vessels. Reactive oxygen species also enhanced vessel reactivity to norepinephrine, which was blocked by RhoA kinase inhibition. Treatment of arteries with reactive oxygen species increased RhoA kinase activity 3-fold, whereas culture of human vascular smooth muscle cells with angiotensin II and activated neutrophils or reactive oxygen species resulted in phosphorylation of key proteins in the RhoA kinase pathway. We conclude that enhanced vascular reactivity of omental arteries in preeclampsia is due to reactive oxygen species activation of the RhoA kinase pathway, and that enhanced vascular reactivity is likely due to the infiltration of neutrophils. We speculate that neutrophil infiltration into systemic vasculature of preeclamptic women is an important mechanism for hypertension.