Elevated steady-state bladder preload activates myosin phosphorylation: detrusor smooth muscle is a preload tension sensor

Abstract

In rabbit bladder wall (detrusor) muscle, the degree of tone induced during physiological filling (filling tone) is the sum of adjustable preload tension and autonomous contractile tension. The present study was designed to determine whether the level of filling tone is dependent on detrusor muscle length. Maximum active tension induced by KCl was parabolic in relation to length [tension increased from 70% to 100% of a reference length (L(ref)) and decreased at longer muscle lengths]. Filling tone, however, increased in a linear fashion from 70% to 120% L(ref). In the presence of ibuprofen to abolish autonomous contraction and retain adjustable preload tension, tension was reduced in strength but remained linearly dependent on length from 70% to 120% L(ref). In the absence of autonomous contraction, stretching detrusor muscle from 80% to 120% L(ref) still caused an increase in tone during PGE(2)-induced rhythmic contraction, suggesting that muscle stretch caused increases in detrusor muscle contractile sensitivity rather than in prostaglandin release. In the absence of autonomous contraction, the degree of adjustable preload tension and myosin phosphorylation increased when detrusor was stretched from 80% to 120% L(ref), but also displayed length-hysteresis, indicating that detrusor muscle senses preload rather than muscle length. Together, these data support the hypothesis that detrusor muscle acts as a preload tension sensor. Because detrusor muscle is in-series with neuronal mechanosensors responsible for urinary urgency, a more thorough understanding of detrusor muscle filling tone may reveal unique targets for therapeutic intervention of contractile disorders such as overactive bladder.