Enhanced renal function in bradykinin B(2) receptor transgenic mice.
Enhanced renal function in bradykinin B(2) receptor transgenic mice.
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DOI：
10.1152/ajprenal.2000.278.3.f484
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发表时间：
2000-03
期刊：
影响因子：
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通讯作者：
D. Wang;H. Yoshida;Q. Song;L. Chao;J. Chao
中科院分区：
文献类型：
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作者：
D. Wang;H. Yoshida;Q. Song;L. Chao;J. Chao
组织激肽释放酶-激动素系统被认为是一种旁分泌和/或自分泌激素系统，调节动脉压、肾脏血流动力学和电解质排泄。我们已经建立了一个过度表达人缓激肽B(2)受体的转基因小鼠模型，小鼠出现了终生低血压。通过这个动物模型，我们进一步分析了B(2)受体在调节肾功能中的潜在作用。转基因小鼠的基线尿排泄、尿钾排泄和pH显著增加，而尿钠排泄和血钠浓度没有改变。转基因小鼠的肾脏血流量、肾小球滤过率和尿流量增加。与对照小鼠相比，转基因小鼠的肾功能增强伴随着尿硝酸盐/亚硝酸盐、cGMP和cAMP水平的显著增加，而尿激肽水平没有改变。转基因小鼠肾脏cGMP和cAMP含量也显著增加。由于肾素-血管紧张素系统对激肽释放酶-激动素系统的血管收缩起缓冲作用，所以用Northern印迹法检测肾素-血管紧张素组分的表达。我们发现，在B(2)受体转基因小鼠中，肝脏血管紧张素原的表达显著增加，而肾脏肾素和肺血管紧张素转换酶的mRNA水平没有变化。这些研究表明，转基因小鼠中B(2)受体的过度表达通过激活一氧化氮-cGMP和cAMP信号转导通路而导致低血压和肾功能增强。
The tissue kallikrein-kinin system has been recognized as a paracrine and/or autocrine hormonal system that regulates arterial pressure, renal hemodynamics, and electrolyte excretion. We have created a transgenic mouse model overexpressing human bradykinin B(2) receptor, and the mice developed lifetime hypotension. With this animal model, we further analyzed the potential role of B(2) receptors in regulation of renal function. Baseline urinary excretion, urinary potassium excretion, and pH were significantly increased in transgenic mice, whereas urinary sodium excretion and serum sodium concentration were unaltered. Transgenic mice exhibited increased renal blood flow, glomerular filtration rate, and urine flow. Enhanced renal function was accompanied by significant increases in urinary nitrate/nitrite, cGMP, and cAMP levels with unaltered urinary kinin levels in transgenic mice compared with control siblings. Renal cGMP and cAMP content was also significantly increased in transgenic mice. Because the renin-angiotensin system exerts vasoconstriction buffering vasodilation of the kallikrein-kinin system, expression of renin-angiotensin components was examined by Northern blot analysis. We found a significant increase in hepatic angiotensinogen expression with no changes in renal renin and pulmonary angiotensin-converting enzyme mRNA levels in B(2) receptor transgenic mice. These studies showed that overexpression of B(2) receptors in transgenic mice resulted in hypotension and enhanced renal function through activation of nitric oxide-cGMP and cAMP signal transduction pathways.