Increased genetic susceptibility to renal damage in the stroke-prone spontaneously hypertensive rat
Increased genetic susceptibility to renal damage in the stroke-prone spontaneously hypertensive rat
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DOI：
10.1046/j.1523-1755.2002.00321.x
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发表时间：
2002-05-01
影响因子：
19.6
通讯作者：
Bidani, AK
中科院分区：
文献类型：
--
作者：
Churchill, PC;Churchill, MC;Bidani, AK
背景。补充盐后，自发性高血压大鼠（SHR）的肾损害比卒中易感大鼠（SHRsp）的肾损害要小得多，并提出这些菌株对肾损害的遗传易感性存在差异。然而，无线电遥测血压测量表明，盐补充导致SHRsp中更严重和加速的高血压。因此，目前尚不清楚肾脏损害的差异是由于血压暴露的不同，还是由于肾脏对高血压损害的内在（遗传）易感性的真正差异。在未切除肾的受者中，在SHR和SHRsp株之间进行肾交叉移植，以便研究SHR和SHRsp肾脏在同一宿主中，暴露于相同的BP谱和代谢环境中对肾损伤的易感性。移植后，在给予8% NaCl饮食加速高血压和肾损害之前和之后，用无线电遥测法监测血压。然后切除肾脏，进行肾损害组织学评估。在SHR受者中，供体肾脏表现出比对侧天然SHR肾脏更严重的高血压损害，但组织学证据表明，轻微的细胞免疫排斥反应也可能促进了肾损害的增加。然而，即使在SHRsp受者中，天然SHRsp肾脏表现出的损害是对侧移植SHR肾脏的两倍。这些数据明确表明，当暴露于完全相同的血压和代谢环境时，SHRsp肾脏本质上比SHR肾脏更容易受到肾脏损害。
Background. The spontaneously hypertensive rat (SHR) develops much less renal damage than the stroke-prone strain of SHR (SHRsp) after salt-supplementation, and it has been proposed that these strains differ in their genetic susceptibility to renal damage. However, radiotelemetric BP measurements have shown that salt-supplementation results in more severe and accelerated hypertension in the SHRsp. Therefore, it is unclear whether the differences in renal damage are due to differences in BP exposure or true differences in intrinsic (genetic) renal susceptibility to hypertensive damage.Methods. Kidney cross transplantation was performed between the SHR and SHRsp strains in uninephrectomized recipients to allow an investigation of the susceptibility to renal damage in SHR and SHRsp kidneys maintained in the same host and exposed to the same BP profile and metabolic environment. Following transplantation, BP was radiotelemetrically monitored before and after an 8% NaCl diet given to accelerate hypertension and renal damage. Then the kidneys were removed and renal damage was assessed histologically.Results. In the SHR recipients, the SHRsp donor kidneys exhibited more hypertensive damage than the contralateral native SHR kidneys, but histologic evidence of mild cellular immunologic rejection also was observed that could have facilitated the increased renal damage, However, even in SHRsp recipients, the native SHRsp kidneys exhibited twice the damage seen in the contralateral transplanted SHR kidneys.Conclusion. These data unequivocally demonstrate that the SHRsp kidneys are intrinsically more susceptible than the SHR kidneys to renal damage when exposed to exactly the same BP and metabolic environment.