el-Dahr S, Yosipiv I V, Muchant D G, Chevalier R L
Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Am J Physiol. 1996 Mar;270(3 Pt 2):F425-31. doi: 10.1152/ajprenal.1996.270.3.F425.
The mechanisms involved in the postnatal induction of renal kallikrein gene transcription and enzymatic activity are unknown. The present study was designed to test the hypothesis that salt (NaCl) intake regulates the ontogeny of renal kallikrein gene expression and enzymatic activity and urinary kallikrein excretion. Newborn rats were artificially fed via a gastric tube with a milk formula containing either normal (25 meq/l, same as in maternal milk) or high (145 meq/l) NaCl content from day 7 to 14 of postnatal life. High-salt feeding decreased renal kallikrein mRNA levels (P < 0.05) and kallikrein-like activity (P < 0.05) compared with rat pups on normal salt intake. However, urinary kallikrein excretion (Ukal) was not different on chronic high vs. normal salt intake. Furthermore, acute volume expansion (0.9% saline, 1% body wt iv) did not alter Ukal in either group of developing rats. In adult rats, 1% NaCl in the drinking water for 10 days decreased renal active kallikrein contents (P < 0.05) but did not alter kallikrein mRNA levels compared with pair-fed rats on normal salt diet. Acute volume expansion in adult rats decreased active Ukal in the high-salt group only (P < 0.05). High-salt feeding upregulated bradykinin B2 receptor mRNA in the developing rats (P < 0.05). We conclude that chronic salt loading suppresses the postnatal rise in renal kallikrein gene expression and enzymatic activity, indicating that sodium intake is an important factor in the maturation of renal kallikrein synthesis. The data also suggest that bradykinin B2 receptor gene expression in the developing kidney may be subject to reciprocal feedback regulation by endogenous kallikrein-kinin activity.
出生后肾脏激肽释放酶基因转录和酶活性诱导所涉及的机制尚不清楚。本研究旨在验证以下假设：盐（氯化钠）摄入量调节肾脏激肽释放酶基因表达、酶活性及尿激肽释放酶排泄的个体发生。从出生后第7天至14天，通过胃管人工喂养新生大鼠，所用奶粉中氯化钠含量分别为正常水平（25毫当量/升，与母乳相同）或高水平（145毫当量/升）。与正常盐摄入的幼鼠相比，高盐喂养降低了肾脏激肽释放酶mRNA水平（P<0.05）和激肽释放酶样活性（P<0.05）。然而，慢性高盐摄入与正常盐摄入时的尿激肽释放酶排泄没有差异。此外，急性容量扩张（0.9%生理盐水，静脉注射1%体重）在两组发育中的大鼠中均未改变尿激肽释放酶排泄。在成年大鼠中，与正常盐饮食的配对喂养大鼠相比，饮水中1%氯化钠持续10天降低了肾脏活性激肽释放酶含量（P<0.05），但未改变激肽释放酶mRNA水平。成年大鼠急性容量扩张仅使高盐组的活性尿激肽释放酶降低（P<0.05）。高盐喂养上调了发育中大鼠的缓激肽B2受体mRNA（P<0.05）。我们得出结论，慢性盐负荷抑制出生后肾脏激肽释放酶基因表达和酶活性的升高，表明钠摄入是肾脏激肽释放酶合成成熟的重要因素。数据还表明，发育中肾脏的缓激肽B2受体基因表达可能受内源性激肽释放酶-激肽活性的相互反馈调节。
