RENAL-FUNCTION AFTER RELEASE OF URETERAL OBSTRUCTION - ROLE OF ENDOTHELIN AND THE RENAL-ARTERY ENDOTHELIUM

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) are decreased and mean arterial pressure (MAP) is increased after unilateral release of bilateral ureteral obstruction (BUO). An imbalance between vasoconstrictor and vaso dilator substances may explain the hemodynamic alterations seen in this setting. The present study examines the role of endothelin-1 in such alterations. Rats with BUO (N = 10) had significantly lower GFR and ERPF (ml/min/kg body wt) than sham-operated rats (SOR, N = 9) (1.40 +/- 0.14 vs. 6.20 +/- 0.38 and 5.12 +/- 0.68 vs. 20.2 +/- 2.20, respectively) and significantly higher MAP (mm Hg) than SOR (154.9 +/- 3.2 vs. 120.6 +/-1.7). Rats with BUO given a specific antiendothelin antibody (N = 8) had significantly higher GFR (2.10 +/- 0.12) and ERPF (7.46 +/- 0.95) than BUO control rats, but there were no significant changes in MAP (159.5 +/- 5.8). In SOR (N = 6), mechanical denudation of the main renal artery endothelium did not significantly affect renal function when compared to renal function in control SOR. However, the same maneuver significantly lowered GFR (0.64 +/- 0.17) and ERPF (1.67 +/- 0.36) in BUO rats (N = 5) when compared to BUO control rats. We conclude that: (1) endothelin-1 has a significant vasoconstrictor role in rats with BUO of 24 hours duration and accounts for a portion of the decrease in glomerular filtration rate seen in rats after unilateral release of bilateral ureteral obstruction, and (2) in the BUO setting, the net role of the renal artery endothelium is vasodilatory.