Enhancement of rat bladder contraction by artificial sweeteners via increased extracellular Ca2+ influx

Introduction: Consumption of carbonated soft drinks has been shown to be independently associated with the development of overactive bladder symptoms (OR 1.62, 95% CI 1.18, 2.22) [Dallosso, H.M., McGrother, C.W., Matthews, R.J., Donaldson, M.M.K., 2003. The association of diet and other lifestyle factors with overactive bladder and stress incontinence: a longitudinal study in women. BJU Int. 92, 69-77]. We evaluated the effects of three artificial sweeteners, acesulfarne K, aspartame and sodium saccharin, on the contractile response of isolated rat detrusor muscle strips. Methods: Strips of detrusor muscle were placed in an organ bath and stimulated with electrical field stimulation (EFS) in the absence and presence of atropine, and with alpha,beta methylene ATP, potassium, calcium and carbachol. Results: Sweeteners 10(-7) M to 10(-2) M enhanced the contractile response to 10 Hz EFS cornpared to control (p < 0.01). The atropine-resistant response to EFS was marginally increased by acesulfame K 10(-6) M, aspartame 10(-7) M and sodium saccharin 10(-7) M. Acesulfame K 10-6 M increased the maximum contractile response to alpha,beta methylene ATP by 35% ( 9.6%) (p < 0.05) and to KCl by 12% ( 3.1%) (p < 0.01). Sodium saccharin also increased the response to KCl by 37% ( 15.2%) (p < 0.05). These sweeteners shifted the calcium concentration-response curves to the left. Acesulfaine K 10-6 M increased the log EC50 from -2.79 ( 0.037) to -3.03 ( 0.048,p < 0.01) and sodium saccharin 10-7 M from -2.74 ( +/- 0.03) to 2.86 (+/- 0.031, p < 0.05). The sweeteners had no significant effect on the contractile response to carbachol but they did increase the amplitude of spontaneous bladder contractions. Discussion: These results suggest that low concentrations of artificial sweeteners enhanced cletrusor muscle contraction via modulation of L-type Ca+2 channels. (c) 2006 Elsevier Inc. All rights reserved.