Obstruction Alters the Effect of Prostaglandin E2 on Ureteral Contractility

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Abstract
Background and Purpose: Although our understanding of ureteral physiology during acute obstruction remains limited, we believe that prostanoids (prostaglandins [PGs], thromboxanes, prostacyclins) play a major role in modulation of ureteral contractility and that inhibition of prostanoid synthesis causes substantial reduction in in-vitro and in-vivo ureteral contractility rates. The purpose of this study was to determine the in-vitro effects of PGE2 on chronically obstructed human and acutely obstructed porcine ureters. Materials and Methods: Female pigs underwent unilateral laparoscopic ureteral obstruction. Following 1, 2, 6, 24, and 48 hours of obstruction (n = 3 at all points), animals were euthanized, and obstructed, contralateral nonobstructed, and normal (from unobstructed pigs) ureters were harvested. Chronically obstructed human ureter was obtained from subjects who underwent nephrectomy to remove nonfunctioning kidneys. Normal human ureter was obtained from the discarded portion of excess distal ureter in patients undergoing elective donor nephrectomy. Rings 4 to 5 mm long were suspended in aerated Krebs buffer, and their spontaneous contractions and contraction in response to various concentrations of PGE2 were recorded. Results: Prostaglandin E2 increased contractility in chronically obstructed human ureters. In acutely obstructed porcine ureteral segments, low concentrations of PGE2 inhibited ureteral contractility in a dose-dependent fashion, similar to controls. At higher concentrations of PGE2, contractility was increased. This increase was more pronounced with longer intervals of obstruction in a time-dependent manner. Conclusion: Prostaglandin E2 increased contractility in obstructed ureters while relaxing normal and nonobstructed ureters. The response to PGE2 was accentuated by a longer duration of obstruction. ProstaglandinE2 may be a unique target for pharmacologic modulation in the treatment of symptoms associated with acute urinary obstruction.