Modulation of Endothelin Family Gene Expression in Renal Hypertrophy

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Abstract
The present study was designed to assess how the renal expression of mRNA for endothelin (ET) families is regulated during compensatory renal hypertrophy in rats. ET family gene expression was studied in the contralateral kidney of uninephrectomized and sham-operated rats. Rats were sacrificed at 0, 1, 3, 6, 12, adn 24 h after unilateral nephrectomy of the sham operation. Three hours after the left nephrectomy, ET-1 and ET receptor B mRNA levels in the renal cortex increased significantly (ET-1, 10.6-fold compared to those in sham-operated rats, p < 0.001, and ET receptor B, 6.8-fold, p < 0.001), and then decreased gradually to the control level after 24 h; in contrast, ET-3 and ET receptor A mRNA levels demonstrated little change throughout the experiment. We additionally measured the plasma ET concentration and renal ET-1 production following unilateral nephrectomy. ET-1 levels in the renal cortex increased gradually, with a peak 6 h after nephrectomy (3.6-fold compared to those in sham-operated rats, p < 0.01), and then decreased to the control level after 24 h. However, plasma ET-1 levels demonstrated little change until after 24 h. The glomerular expression of ET-1 and ET receptors A and B mRNA demonstrated minimal change throughout the experimental period. Glomerular ET-3 mRNA expression were detected in neither the unilateral nephrectomy nor the sham-operated rats. Our results indicate that the time course of the mRNA expression of ET-1 and ET receptor B differs from that of ET-3 and ET receptor A in the renal cortex, and that glomerular mRNA levels for ET families are not associated with renal hypertrophy in the early stages following unilateral nephrectomy.

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