POST-TRANSPLANT HYPERTENSION IN THE RAT - EFFECTS OF CAPTOPRIL AND NATIVE NEPHRECTOMY
POST-TRANSPLANT HYPERTENSION IN THE RAT - EFFECTS OF CAPTOPRIL AND NATIVE NEPHRECTOMY
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DOI：
10.1038/ki.1989.157
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发表时间：
1989-07-01
影响因子：
19.6
通讯作者：
KLOTMAN, PE
中科院分区：
文献类型：
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作者：
COFFMAN, TM;HIMMELSTEIN, S;KLOTMAN, PE
在功能良好的同种异体肾移植患者中，病变的自体肾的存在似乎是血压升高的常见原因。我们使用大鼠模型评估了自体肾在移植后高血压中的作用，在该模型中，排斥反应和免疫抑制的混杂变量可以被消除。为了在天然肾脏中产生疾病，对PVG大鼠进行5/6肾切除术。肾消融术后4周，这些高血压动物移植了来自同系PVG供体的肾脏。4周后，观察开搏通和自体肾切除对血压和肾血流动力学的影响。接受非排斥性同种肾移植的残留自体肾动物出现持续高血压、血浆肾素水平升高和移植功能降低。在这些动物中，给予卡托普利降低了全身血压。尽管血压降低，但移植肾对PAH的清除率显著增加，而GFR略有上升。切除残余的自体肾也能显著降低血压。然而，与巯甲丙脯酸相比，自体肾切除术产生了更显着的GFR增加，而不显着影响肾血流量。在该大鼠移植后高血压模型中，血压升高和同种移植物功能降低是由患病的天然肾脏介导的，部分是通过血管紧张素II的作用。这些数据表明，血管紧张素转换酶抑制剂和自体肾切除术可能对自体肾引起的移植后高血压患者有有益的血流动力学作用。
In patients with well-functioning renal allografts, the presence of diseased native kidneys appears to be a common cause of elevated blood pressure. We evaluated the role of native kidneys in post-transplant hypertension using a rat model in which the confounding variables of rejection and immunosuppression could be eliminated. To produce disease in native kidneys, PVG rats were subjected to 5/6 nephrectomy. Four weeks following renal ablation, these hypertensive animals were transplanted with kidneys from syngeneic PVG donors. Four weeks later, the effects of captopril and native nephrectomy on blood pressure and renal hemodynamics were examined. Animals with remnant native kidneys which received non-rejecting renal isografts had sustained hypertension, elevated plasma renin levels and reduced transplant function. In these animals, administration of captopril reduced systemic blood pressure. Despite the reduction in blood pressure, PAH clearance by the transplanted kidney increased markedly while GFR rose modestly. Removal of the remnant native kidney also acutely lowered blood pressure. However, compared to captopril, native nephrectomy produced a more marked increase in GFR without significantly affecting renal blood flow. In this model of post-transplant hypertension in the rat, elevated blood pressure and reduced isograft function are mediated by the diseased native kidney, in part through the effects of angiotensin II. These data suggest that ACE inhibitors and native nephrectomy may have beneficial hemodynamic effects in patients with post-transplant hypertension caused by native kidneys.