Role of Inflammation and the Angiotensin Type 2 Receptor in the Regulation of Arterial Pressure During Pregnancy in Mice
Role of Inflammation and the Angiotensin Type 2 Receptor in the Regulation of Arterial Pressure During Pregnancy in Mice
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DOI：
10.1161/hypertensionaha.114.03189
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发表时间：
2014-09-01
期刊：
影响因子：
8.3
通讯作者：
Denton, Kate M.
中科院分区：
文献类型：
--
作者：
Mirabito, Katrina M.;Hilliard, Lucinda M.;Denton, Kate M.
在正常妊娠期间，肾素-血管紧张素系统被激活，但孕妇对血管紧张素II的升压作用有抵抗力。我们的目的是确定血管紧张素2型受体（AT（2）R）在妊娠期间动脉压、尿钠排泄和免疫细胞浸润调节中的作用。通过遥测测量平均动脉压，并使用流式细胞术计数妊娠期间14周龄野生型和AT（2）R敲除小鼠的免疫细胞浸润。在野生型小鼠中，平均动脉压在妊娠期间下降，在妊娠第9天达到最低点（-6 +/- 2 mm Hg），并在妊娠后期恢复到接近孕前水平。在AT（2）R缺陷小鼠中，不存在妊娠中期平均动脉压下降。此外，平均动脉压显着增加，在妊娠后期与野生型小鼠相比（约10毫米汞柱）。正如预期的那样，循环免疫细胞活化在怀孕期间受到抑制。然而，这种反应在AT（2）R缺陷小鼠中不存在。虽然肾脏免疫细胞浸润在基因型之间是相似的，但在AT（2）R缺陷小鼠中，T细胞表型向促炎性辅助性T细胞1表型转变。这些数据表明，AT（2）R在动脉血压调节中起着重要作用，并可能调节妊娠期间T细胞活化和肾脏细胞因子的产生。因此，AT（2）R表达的缺陷可能有助于妊娠高血压，因此代表了一个潜在的治疗靶点。
During normal pregnancy the renin-angiotensin system is activated, yet pregnant women are resistant to the pressor effects of angiotensin II. Our aim was to determine the role of the angiotensin type 2 receptor (AT(2)R) in the regulation of arterial pressure, natriuresis, and immune cell infiltration during pregnancy. Mean arterial pressure was measured via telemetry, and flow cytometry was used to enumerate immune cell infiltration in 14-week-old wild-type and AT(2)R knockout mice during gestation. In wild-type mice, mean arterial pressure decreased during gestation, reaching a nadir at gestational day 9 (-6 +/- 2 mm Hg) and returned to near preconception levels during late gestation. In AT(2)R-deficient mice, the midgestational decrease in mean arterial pressure was absent. Furthermore, mean arterial pressure was significantly increased during late gestation compared with wild-type mice (approximate to 10 mm Hg). As expected, circulating immune cell activation was suppressed during pregnancy. However, this response was absent in AT(2)R-deficient mice. While renal immune cell infiltration was similar between the genotypes, there was a significant T cell phenotypic switch toward a proinflammatory T-helper 1 phenotype in AT(2)R-deficient mice. These data indicate that the AT(2)R plays an important role in arterial pressure regulation and may modulate T cell activation and renal cytokine production during pregnancy. Therefore, deficits in AT(2)R expression may contribute to pregnancy-induced hypertension and thus represents a potential therapeutic target.