Kurtz T W, Simonet L, Kabra P M, Wolfe S, Chan L, Hjelle B L
Department of Laboratory Medicine, University of California, San Francisco 94143.
J Clin Invest. 1990 Apr;85(4):1328-32. doi: 10.1172/JCI114572.
The spontaneously hypertensive rat (SHR) exhibits alterations in the renin-angiotensin-aldosterone system which are similar to those that characterize patients with "nonmodulating" hypertension, a common and highly heritable form of essential hypertension. Accordingly, we determined whether the inheritance of a DNA restriction fragment length polymorphism (RFLP) marking the renin gene of the SHR was associated with greater blood pressure than inheritance of a RFLP marking the renin gene of a normotensive control rat. In an F2 population derived from inbred SHR and inbred normotensive Lewis rats, we found the blood pressure in rats that inherited a single SHR renin allele to be significantly greater than that in rats that inherited only the Lewis renin allele. To the extent that the SHR provides a suitable model of "nonmodulating" hypertension, these findings raise the possibility that a structural alteration in the renin gene, or a closely linked gene, may be a pathogenetic determinant of increased blood pressure in one of the most common forms of essential hypertension in humans.
自发性高血压大鼠（SHR）的肾素-血管紧张素-醛固酮系统存在改变，这些改变与“非调节性”高血压患者的特征相似，“非调节性”高血压是原发性高血压中一种常见且高度可遗传的形式。因此，我们确定了标记SHR肾素基因的DNA限制性片段长度多态性（RFLP）的遗传是否比标记正常血压对照大鼠肾素基因的RFLP的遗传与更高的血压相关。在由近交SHR和近交正常血压Lewis大鼠衍生的F2群体中，我们发现继承单个SHR肾素等位基因的大鼠的血压显著高于仅继承Lewis肾素等位基因的大鼠。就SHR提供了“非调节性”高血压的合适模型而言，这些发现增加了一种可能性，即肾素基因或紧密连锁基因的结构改变可能是人类最常见的原发性高血压形式之一中血压升高的致病决定因素。
