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 (UNaV) and fractional sodium excretion (FENa) 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), UNaV by 190 +/- 60% (P < 0.001), and FENa 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.


CONCLUSIONS
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.
Hammad
F T
FT
Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin, New Zealand.
Wheatley
A M
AM
Davis
G
G
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D002216:Captopril / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism*; D006977:Hypertension, Renal / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000188:drug therapy / Q000378:metabolism*; D014563:Urodynamics / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D016232:Endothelins; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D002216:Captopril; D000077300:Bosentan