Contractions induced by hypo-osmolar solutions in human detrusor muscle

Introduction: Urine osmolarities vary widely above and below plasma osmolarity. When the mucosa is inflamed it may leak, exposing the muscle to abnormal osmolarities. This study investigates the effect of hypo-osmolar solutions (HOTs) on human detrusor muscle strips. Materials and methods: With ethical approval, human detrusor muscle removed at surgery was dissected into strips (5 × 1 × 1 mm), mounted in an organ bath and perfused with gassed Tyrode's solution (pH 7.36, 36°C, osmolarity 285 mOsmol/L). Isometric tension was recorded via a microstrain gauge transducer. The solution was made hypo-osmolar by removing NaCl. Gadolinium (Gd³⁺). a blocker of stretch activated channels (SACs), and Diltiazem. an L-type Ca²⁺ channel antagonist, were used at 10 μmol/L. The results are expressed as mean (SEM) percentage of maximal tension produced by 1 μmol/L carbachol for each patient. Results: HOTs produced an increase in tension of similar magnitude to 1 μmol/L carbachol. The effect depended on osmolarity rather than ionic strength; a solution of reduced ionic strength made iso-osmolar by mannitol produce no contraction. In paired experiments. Gd³⁺ and Diltiazem significantly reduced the response to HOTs. with values of 108 (25) and 75 (27) (P = 0.004, n = 11) for Gd³⁺, and 69 (11) and 37 (9) (P = 0.001, n = 9) for Diltiazem, respectively. In Ca²⁺-free solution, a response was still present but was significantly reduced, at 65 (10) and 21 (8). respectively (P = 0.001, n = 9), indicating direct mobilization of Ca²⁺ from intracellular stores. Conclusions: HOTs produced a tension increase in detrusor strips that appears to be dependent partly on the release of intracellular Ca²⁺ partly on the influx of Ca²⁺ through L-type Ca²⁺ channels and partly upon SACs.