dinoprost and Urethral-Obstruction

Partial outlet obstruction of the urinary bladder has been demonstrated to induce specific dysfunctions in cellular and sub-cellular membrane structures within the bladder's smooth muscle and mucosal compartments. Recent studies have linked these membrane dysfunctions to alterations in phospholipid metabolism leading to mobilization of free arachidonic acid, the precursor for synthesis of prostaglandins (PG). The purpose of this study was to determine if partial outlet obstruction of the urinary bladder induces changes in the capacity of bladder smooth muscle and mucosa to generate PG. PG were isolated from control and partially obstructed urinary bladder smooth muscle and mucosa of male New Zealand White (NZW) rabbits. PG concentrations (PGE2, PGF2alpha and PGI2, as its stable metabolite 6-keto-PGF1alpha) were determined after 30 minute incubations using enzyme-linked immunoassay (ELISA) kits. In both control and obstructed rabbit urinary bladders, PG generation was significantly higher in isolated mucosa than muscle tissues. A significantly higher concentration of PGF2alpha, and 6-keto-PGF1alpha was measured in obstructed muscle tissue relative to controls. The concentration of 6-keto-PGF1alpha was also significantly higher than the concentrations measured for PGE2 and PGF2alpha in both control and obstructed smooth muscle samples. The generation of PGE2 was significantly higher in rabbit urinary bladder mucosa than either PGF2alpha or 6-keto-PGF1alpha in both control and obstructed samples. The capacity of obstructed mucosal tissue to generate 6-keto-PGF1alpha was significantly higher than control tissue, while no significant differences in PGE or PGF2alpha generation were noted. These data suggest obstruction of the urinary bladder induce specific elevations in PG in both smooth muscle and mucosal tissues.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Dinoprost; Enzyme-Linked Immunosorbent Assay; Male; Mucous Membrane; Muscle, Smooth; Organ Size; Prostaglandins; Prostaglandins E; Rabbits; Urethral Obstruction; Urinary Bladder

A child with post-obstructive urinary concentrating defect was studied for the possible pathophysiological role of prostaglandins and an eventual therapeutic approach. Increased urinary excretion of prostaglandins was corrected by indomethacin, with resultant increased nephrogenous cyclic AMP and partial improvement in the concentrating defect. The addition of a thiazide restored urinary concentration. These results add clinical support to the conception of the important role of prostaglandins in the mechanism of post-obstructive hyposthenuria. This therapeutic regimen is advocated for prolonged post-obstructive concentrating defect.

Topics: Child, Preschool; Dinoprost; Dinoprostone; Humans; Hydrochlorothiazide; Indomethacin; Kidney Concentrating Ability; Male; Polyuria; Postoperative Complications; Prostaglandins E; Prostaglandins F; Urethral Obstruction