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.
Torralbo
A
A
Nephrology Service, San Carlos University Hospital, Madrid, Spain.
Trobo
J I
JI
Borque
M
M
Herrero
J A
JA
Velasco
E
E
Marcello
M
M
González-Mate
A
A
Barrientos
A
A
D000818:Animals; D004656:Enalapril / Q000627:therapeutic use; D016232:Endothelins / Q000378:metabolism / Q000652:urine*; D004921:Erythropoietin / Q000627:therapeutic use; D006977:Hypertension, Renal / Q000188:drug therapy / Q000652:urine*; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000188:drug therapy / Q000652:urine*; D008297:Male; D009392:Nephrectomy; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use; D014700:Verapamil / Q000627:therapeutic use
D016232:Endothelins; D011994:Recombinant Proteins; D004921:Erythropoietin; D004656:Enalapril; D014700:Verapamil