Aberrant renal vascular morphology and renin expression in mutant mice lacking angiotensin-converting enzyme
Aberrant renal vascular morphology and renin expression in mutant mice lacking angiotensin-converting enzyme
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DOI：
10.1161/01.hyp.29.1.216
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发表时间：
1997-01-01
期刊：
影响因子：
8.3
通讯作者：
Gomez, RA
中科院分区：
文献类型：
--
作者：
Hilgers, KF;Reddi, V;Gomez, RA
为了确定血管紧张素转换酶是否在正常肾脏结构的发育和维持中发挥作用，将10至12个月大的转换酶基因破坏纯合子雌性小鼠的肾脏形态与年龄匹配的野生型小鼠进行了比较。肾小管梗阻，扩张和萎缩存在于所有肾脏的纯合子突变型小鼠，但在野生型中不存在;两个肾脏从4个突变型小鼠，但没有从野生型肾积水。与野生型小鼠的脉管系统相比，从没有转化酶的小鼠显微解剖的整个动脉血管树严重扭曲;所有肾内动脉血管增宽和增厚，包括末端（传入）小动脉。在野生型小鼠肾脏中，仅在肾小球定位中检测到肾素阳性细胞。相反，在没有转化酶的小鼠中观察到肾素免疫染色的异常分布;沿动脉血管沿着可见散在的肾素阳性细胞，通常位于血管周围，肾小球周围有间质性肾素阳性细胞。与野生型相比，突变小鼠的肾脏肾素mRNA增加了32倍以上。北方印迹分析表明，这种增加包括大量较小的肾素RNA转录本的积累。总之，缺乏转化酶的小鼠表现出异常的肾血管和肾小管。肾素合成增加，伴随着小的肾素mRNA种类的存在，并且肾素主要存在于间质和血管周围细胞中。我们的结论是，血管紧张素转换酶是必要的，以保持正常的肾脏结构和正常模式的肾素表达。
To determine whether angiotensin-converting enzyme plays a role in the development and maintenance of normal renal architecture, the renal morphology of 10- to 12-month-old female mice homozygous for a disruption of the converting enzyme gene was compared with that of age-matched wild-type mice. Tubular obstruction, dilatation, and atrophy were present in all kidneys from the homozygous mutant mice but absent in wild types; two kidneys from 4 mutant mice but none from the wild types were hydronephrotic. The entire arterial vascular tree, microdissected from mice with no converting enzyme, was grossly distorted in comparison to the vasculature of wild-type mice; all intrarenal arterial vessels were widened and thickened, including the terminal (afferent) arterioles. In wild-type mice kidneys, renin-positive cells were detected exclusively in a juxtaglomerular localization. In contrast, abnormal distribution of renin immunostaining was observed in mice without converting enzyme; scattered renin-positive cells were seen along the arterial vessels, often in a perivascular localization, and interstitial renin-positive cells surrounded glomeruli. Kidney renin mRNA was increased more than 32-fold in the mutant mice compared with wild types. Northern blot analysis revealed that this increase included the accumulation of large amounts of smaller renin RNA transcripts. In summary, mice lacking the converting enzyme exhibit abnormal renal vessels and tubules. Renin synthesis is increased, accompanied by the presence of small renin mRNA species, and renin is present mainly in interstitial and perivascular cells. We conclude that angiotensin-converting enzyme is necessary to preserve normal kidney architecture and the normal pattern of renin expression.