Enhanced expression of renal endothelin-converting enzyme-1 and endothelin-A-receptor mRNA in rats with interstitial fibrosis following ureter ligation

Endothelin-1 (ET-1) has been implicated in many chronic renal glomerular di seases. The purpose of this study was to investigate whether the levels of mRNA expression of endothelin-converting enzyme-1 (ECE-1) and endothclin-A- and -B- (ETA and ETB) receptors are altered during the: progression of int erstitial fibrosis following ureter ligation. Rats were subjected to left u reter ligation or a sham operation and euthanized 5 days afterward. Kidneys were fixed in Carnoy's Fixative, embedded in paraffin, and sectioned for a ssessment of interstitial fibrosis by staining for collagen III using immun ofluorescence techniques. The area occupied by collagen staining was quanti fied by image analysis. Kidneys from obstructed rats showed a 54% increase in the area occupied by collagen III sraining compared to the contralateral kidney, and an 89% increase compared to sham-operated kidneys. The mRNA le vels of ECE-1, as well as ETA- and ETB-receptors in the kidney were analyze d by Northern blots. It was found that the ECE-1 and ETA-receptor mRNA leve ls in kidneys subjected to ureter ligation increased by 92% and 71%, respec tively, when compared with those obtained from the contralateral kidneys. I n contrast, mRNA levels of ETB-receptors were not significantly different b etween 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.