Alterations in renal endothelin production in rats with reduced renal mass

Renal endothelin-1 (ET-1) production is diminished in spontaneously hypertensive rats. An increase has been reported of renal ET-1 production associated with progression of renal disease in rats with reduced renal mass. The purpose of the present study was to investigate the evolution over time of the urinary ET-1 excretion in an experimental model of renal mass reduction not caused by renal infarction. Rats were subjected to 2/3 nephrectomy (right nephrectomy and resection of the lower left renal pole) and thereafter randomly assigned to a no-treatment control group or to treatment with recombinant erythropoietin, recombinant erythropoietin plus verapamil, or recombinant erythropoietin plus enalapril. The urinary ET-1 excretion was decreased by week 16 after nephrectomy as compared with healthy animals and with the levels 6 weeks after nephrectomy. The temporal evolution of urinary ET-1 excretion in the various groups of rats showed a trend toward decrease in all groups except the one receiving enalapril. The urinary ET-1 excretion correlated directly with creatinine clearance and inversely with tubulointerstitial damage. We observed an inverse correlation between urinary ET-1 excretion and arterial blood pressure 16 weeks after nephrectomy. These results indicate that renal ET-1 production decreases with the progression of renal disease and in relation with the severity of tubulointerstitial damage. The decrease in renal ET-1 production might contribute to the development and perpetuation of renal disease-associated arterial hypertension; this situation may be favorably modified by the use of enalapril.