Endothelin-1 (ET-1) has been implicated in many chronic renal glomerular diseases. The purpose of this study was to investigate whether the levels of mRNA expression of endothelin-converting enzyme-1 (ECE-1) and endothelin-A- and -B- (ETA and ETB) receptors are altered during the progression of interstitial fibrosis following ureter ligation. Rats were subjected to left ureter ligation or a sham operation and euthanized 5 days afterward. Kidneys were fixed in Carnoy's fixative, embedded in paraffin, and sectioned for assessment of interstitial fibrosis by staining for collagen III using immunofluorescence techniques. The area occupied by collagen staining was quantified by image analysis. Kidneys from obstructed rats showed a 54% increase in the area occupied by collagen III staining compared to the contralateral kidney, and an 89% increase compared to sham-operated kidneys. The mRNA levels of ECE-1, as well as ETA- and ETB-receptors in the kidney were analyzed by Northern blots. It was found that the ECE-1 and ETA-receptor mRNA levels in kidneys subjected to ureter ligation increased by 92% and 71%, respectively, when compared with those obtained from the contralateral kidneys. In contrast, mRNA levels of ETB-receptors were not significantly different between the two groups. These results suggest that ET-1, through interaction with the ETA-receptors, may play a role in the progression of interstitial fibrosis following ureter ligation.
Address correspondence and reprint requests to David L. Feldman, LSB 2195, Novartis Pharmaceuticals Corp., 556 Morris Ave., Summit, NJ 07901, U.S.A. E-mail: [email protected]
© 2000 Lippincott Williams & Wilkins, Inc.