Heller J, Schubert G, Havlíckova J, Thurau K
Department of Experimental Medicine, Institute for Clinical Experimental Medicine, Prague, Czech Republic.
Pflugers Arch. 1993 Nov;425(3-4):208-12. doi: 10.1007/BF00374168.
It has been shown that genetic hypertension in rats usually "travels with the kidney". To elucidate the mechanism of this phenomenon further, experiments were carried out in the Prague hypertensive (PH) rat, a model of genetic hypertension derived from the Wistar strain, in which a normotensive parallel, the Prague normotensive (PN) rat, was also bred from the same parent pair. Thus, it is possible to transfer organs between both parallels without substantial signs of rejection and without the use of immunosuppressive drugs. Unilateral nephrectomy and transplantation of one kidney between PH and PN rats, did not affect the arterial blood pressure (BP). Transplantation of one kidney from PN rats to bilaterally nephrectomised PH rats normalised the high BP. If a PH rat was left with one original kidney in situ after the transplantation of a "normotensive" kidney, the high BP persisted until the original "hypertensive" kidney was removed. This removal resulted in sustained normalisation of BP. When the development of high BP in the PH rats was prevented for 2 months after weaning by antihypertensive drugs, transplantation of kidneys from these rats to bilaterally nephrectomised PN rats always induced a sustained hypertension in the recipient. These results argue against a role of high-BP-induced damage to the kidney and against an intrinsic increase in the salt-reabsorptive capacity of the tubular epithelium in PH rats. The data support the view that the kidney from PH rats produces a "hypertensinogenic" substance, the secretion of which is genetically determined and is not influenced by the magnitude of the BP.
研究表明,大鼠的遗传性高血压通常“与肾脏相关”。为了进一步阐明这一现象的机制,我们以布拉格高血压(PH)大鼠为实验对象进行了实验,该大鼠是源自Wistar品系的遗传性高血压模型,同时还培育了与之血压正常的对照品系——布拉格正常血压(PN)大鼠,它们来自同一亲本对。因此,有可能在这两个品系之间进行器官移植,而不会出现明显的排斥迹象,也无需使用免疫抑制药物。对PH大鼠和PN大鼠进行单侧肾切除术,并在两者之间移植一个肾脏,并未影响动脉血压(BP)。将PN大鼠的一个肾脏移植到双侧肾切除的PH大鼠体内,可使高血压恢复正常。如果在移植“正常血压”肾脏后,让PH大鼠保留一个原位的原肾,高血压会持续存在,直到切除原有的“高血压”肾脏,血压才会持续恢复正常。当通过抗高血压药物在断奶后2个月内防止PH大鼠出现高血压时,将这些大鼠的肾脏移植到双侧肾切除的PN大鼠体内,总会使受体大鼠出现持续性高血压。这些结果表明,高血压引起的肾脏损伤以及PH大鼠肾小管上皮细胞盐重吸收能力的内在增加,均与高血压的发生无关。这些数据支持以下观点:PH大鼠的肾脏会产生一种“致高血压”物质,其分泌由基因决定,不受血压水平的影响。