Long-term renal effects of unilateral ureteral obstruction and the role of endothelin

Background: Angiotensin II (Ang II) and endothelin (ET) are involved in the alteration of renal function in unilateral ureteral obstruction (UUO). The renal response to Ang II following the reversal of a 24-hour UUO and the effect of ET blockade by bosentan during the time of obstruction were investigated. Methods: Following blockade of the endogenous production of Ang II by captopril, the renal response to Ang II was studied in rats 15 to 18 days after a 24-hour UUO (N = 10) or a sham operation (N = 9) both with (N = 10) and without (N = 8) bosentan treatment in the periobstruction period. Similar studies were performed in another group (N = 9) two months following the reversal of obstruction. Results: In the sham-operated group, Ang II reduced renal blood flow (RBF) by 42 ± 9% (P < 0.01), glomerular filtration rate (GFR) by 30 ± 8% (P < 0.01), urine volume (UV) by 44 ± 9% (P < 0.001), and absolute (U(Na)V) and fractional sodium excretion (FE(Na)) by 52 ± 9% (P < 0.001) and 33 ± 9% (P = 0.054), respectively. In the previously obstructed kidney, Ang II did not change RBF but increased GFR by 106 ± 40% (P < 0.01), UV by 75 ± 21% (P< 0.001), U(Na)V by 190 ± 60% (P < 0.001), and FE(Na) by 40 ± 13% (P < 0.05). Bosentan treatment in the obstructed group prevented these Ang II-induced effects and did not have any effect on the sham-operated kidney. Two months following reversal of the obstruction, the response of the kidney was similar to that of the control kidney. Conclusion: Twenty-four- hour UUO results in a temporary abnormality in the renal response to Ang II, which is due, in part, to the actions of ET at the time of obstruction.