Applicants Effect of Diet on Metabolic Phenotype-Induced Changes in Bladder Outlet Obstruction in Male Wistar Rats

A concluded study revealed that dietary macronutrient composition of food influenced detrusor smooth muscle hypertrophy and contraction in male Wistar rats with normal and obstructed bladders. The efficacy of the method had been established, this study was then designed to determine the possible reversal of the effects of diet-induced metabolic phenotypes on bladder morphology and function by reversal to a standard diet. Grouped animals were fed for 8 weeks on Control, High Carbohydrate (HCD, High Fat (HFD), and High Protein diets. Partial bladder outlet obstruction was induced, with further feeding for 4 weeks after induction. Animals in each group were then fed on the control diet for 8 weeks, after which they were sacrificed. Bladder weight, smooth muscle/collagen ratio, detrusor contractile activity, Rho-kinase and Myosin Light Chain Kinase were assessed in bladder tissue. Bladder weight was significantly lower in obstructed bladders of rats fed with the HFD and HPD, while smooth muscle/collagen ratio was lower only in the HFD-fed rats (both unobstructed and obstructed bladders). Obstructed HFD bladders reflected a significant increase in detrusor contractility following reversal, bladders of HFD-fed and HPD-BOO animals also showed an increase in contractility, while the HCD-BOO had reduced contractility. In both obstructed and unobstructed bladders of rats fed with HCD, there was a significant lowering of Rho-kinase and MLCK activity back to control values. There was an increase in Rho-kinase I activity in HFD-BOO bladders back to control values. The results of this study suggest that reversal to the control diet causes a corresponding reversal of diet-induced changes in bladder structure and function back to values similar to those obtained in control.