Field L J, Veress A T, Steinhelper M E, Cochrane K, Sonnenberg H
Cold Spring Harbor Laboratory, New York 11724.
Am J Physiol. 1991 Jan;260(1 Pt 2):R1-5. doi: 10.1152/ajpregu.1991.260.1.R1.
Transgenic mice, created from inbred C3HeB/FeJ embryos, were used to overexpress selectively in the liver a fusion gene comprising mouse transthyretin (TTR) regulatory and atrial natriuretic factor (ANF) structural sequences. Animals were anesthetized, and kidney function was studied before and after blood volume expansion. Baseline urine volumes and electrolyte excretions were not significantly different from those of non-transgenic littermates, despite a markedly lower arterial blood pressure in the experimental group. A slightly lower glomerular filtration rate (GFR) in transgenics was not different statistically. Plasma ANF levels measured by radioimmunoassay were approximately 10-fold higher in the transgenic animals, compared with their nontransgenic siblings. After acute blood volume expansion, the diuretic, natriuretic, kaliuretic, and chloruretic responses were markedly enhanced in the transgenic group. Arterial pressure was increased as a result of hypervolemia, although it remained relatively depressed relative to the controls. GFR again was not different. We conclude that transgenic mice overexpressing ANF can maintain normal excretion of salt and water, possibly via ANF-induced reduction of renal perfusion pressure. After acute blood volume expansion, an increase in pressure may allow full renal expression of the chronically elevated ANF levels.
由近交系C3HeB/FeJ胚胎培育出的转基因小鼠，被用于在肝脏中选择性地过度表达一种融合基因，该融合基因包含小鼠甲状腺素运载蛋白（TTR）调控序列和心钠素（ANF）结构序列。动物被麻醉，在血容量扩充前后对肾功能进行了研究。尽管实验组的动脉血压明显较低，但基线尿量和电解质排泄与非转基因同窝仔畜并无显著差异。转基因小鼠的肾小球滤过率（GFR）略低，但在统计学上并无差异。通过放射免疫测定法测得的转基因动物血浆心钠素水平比其非转基因同胞高约10倍。急性血容量扩充后，转基因组的利尿、利钠、利钾和利氯反应明显增强。由于血容量过多，动脉压升高，尽管相对于对照组仍相对较低。肾小球滤过率再次无差异。我们得出结论，过度表达心钠素的转基因小鼠可能通过心钠素诱导的肾灌注压降低来维持盐和水的正常排泄。急性血容量扩充后，血压升高可能使长期升高的心钠素水平在肾脏充分表达。
