Hypertriglyceridemia Impairs Urethral Spontaneous Tone Through Down-regulation of ANO1 in Mouse Urethral Smooth Muscle Cells

Abstract

ObjectiveTo investigate the effect of hypertriglyceridemia (HTG) on the Anoctamin 1 (ANO1)-centered signal on urinary incontinence. MethodsFemale mice were fed with high fat diet to set up HTG mice model. ANO1 expression in urethrae were detected by Flow Cytometry and Western Blotting. The habit of micturition was recorded through urine spot test. Urethral Smooth Muscle Myography was used to record the urethral spontaneous tone (STT) and contraction. Patch-clamp Recording confirmed the currents of ANO1 in urethral smooth muscle cells. ResultsHTG mice showed almost abolished STT and significantly decreased contraction induced by EACT. Meanwhile, a change in urination habits was detected in HTG mice which suggested that mice could not hold the urethral pressure. Furthermore, ANO1 expression in single urethral smooth muscle cells from HTG mice decreased almost 30% than that found in cells from normal group. Moreover, EACT (an N-aroylaminothiazole, ANO1 activator) induced decreased intracellular calcium ([Ca2+]i) and currents in single urethral smooth muscle cells from HTG mice. ConclusionThese results suggested that hypertriglyceridemia decreased the STT on urethral motility by down-regulating the expression of ANO1 in urethral smooth muscles. These findings provide a new perspective on the mechanism of urinary incontinence which is common in HTG patients.