Endogenous sodium pump inhibitors, diabetes mellitus and preeclampsia Preliminary observations and a hypothesis.
Endogenous sodium pump inhibitors, diabetes mellitus and preeclampsia Preliminary observations and a hypothesis.
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DOI：
10.1016/j.pathophys.2007.09.003
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发表时间：
2007-12-01
期刊：
影响因子：
--
通讯作者：
Bagrov, Alexei Y
中科院分区：
文献类型：
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作者：
Bagrov, Yakov Y;Manusova, Natalia B;Bagrov, Alexei Y
内源性Na/K-ATP酶抑制剂（NKA）和糖尿病（DM）是先兆子痫和NaCl敏感性高血压的危险因素。我们的目标是测试这一假设，即NaCl补充，诱导先兆子痫样症状的妊娠大鼠糖尿病通过刺激海蟾毒配基（MBG），钠尿和血管收缩抑制剂的NKA。在雌性Sprague-Dawley大鼠中通过在产后第4天给予65 mg/kg链脲佐菌素诱导2型糖尿病。在完整的大鼠中，妊娠与MBG水平的两倍增加和葡萄糖耐量的轻度损害相关。与正常妊娠大鼠相比，糖尿病妊娠大鼠表现出巨大胎儿，糖耐量受损更严重，MBG水平更高。与完整妊娠大鼠相比，糖尿病妊娠大鼠（在妊娠第12-19天饮用1.8% NaCl）补充NaCl与收缩压升高、胎儿和胎盘重量降低、MBG排泄升高5倍以及红细胞中NKA抑制42%相关。在非妊娠大鼠中，在口服葡萄糖耐量试验中，抗MBG抗体体内预处理产生了夸大的血浆葡萄糖和胰岛素水平的反应。这些结果表明，MBG是糖尿病和先兆子痫发病机制中的共同因素，调节糖耐量可能是内源性强心类固醇的生理功能之一。
Endogenous inhibitors of the Na/K-ATPase (NKA) and diabetes mellitus (DM) are both risk factors for preeclampsia and NaCl sensitive hypertension. Our goal was to test the hypothesis that NaCl supplementation, induces preeclampsia-like symptoms in pregnant rats with DM via stimulation of marinobufagenin (MBG), a natriuretic and vasoconstrictor inhibitor of the NKA. Type 2 DM in female Sprague-Dawley rats was induced by administration of 65mg/kg streptozotocin at day 4 post-partum. In intact rats, pregnancy was associated with a twofold increase in MBG levels and a mild impairment in glucose tolerance. Pregnant rats with DM exhibited fetal macrosomia, greater impairment of glucose tolerance, and higher levels of MBG as compared to that in normal pregnant rats. As compared to intact pregnant rats, NaCl supplementation of diabetic pregnant rats (drinking 1.8% NaCl during days 12-19 of pregnancy) was associated with an increase in systolic blood pressure, decreased fetal and placental weight, fivefold elevation of MBG excretion, and 42% inhibition of NKA in erythrocytes. In nonpregnant rats, in vivo pretreatment with anti-MBG antibody produced an exaggerated response of plasma levels of glucose and insulin in oral glucose tolerance test. These results suggest that MBG is a common factor in the pathogenesis of DM and preeclampsia, and that regulation of glucose tolerance may be one of the physiological functions of endogenous cardiotonic steroids.