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1 Department of Mechanical Engineering, Virginia Commonwealth University, Richmond, VA, USA
2 Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA
3 Departments of Biochemistry and Pediatrics, Virginia Commonwealth University, Richmond, VA, USA
* To whom correspondence should be addressed. E-mail: phratz{at}vcu.edu.
Passive mechanical properties of strips of rabbit detrusor smooth muscle were examined and found by cyclic loading in a calcium-free solution to display viscoelastic softening and strain-induced stress softening (strain softening). Strain softening, or the Mullins effect, is a loss of stiffness attributed to the breakage of crosslinks, and appeared irreversible in detrusor even after the return of spontaneous rhythmic tone during 120 min of incubation in a calcium-containing solution. However, three min of KCl or carbachol (CCh)-induced contraction permitted rapid regeneration of the passive stiffness lost to strain softening, and 3 µM of the RhoA kinase (ROK) inhibitor, Y-27632, prevented this regeneration. The degree of ROK-induced passive stiffness was inversely dependent on muscle length over a length range where peak CCh-induced force was length-independent. Thus, rabbit detrusor displayed variable passive stiffness both strain-history and activation-history dependent. In conclusion, activation of ROK by KCl or CCh increased passive stiffness softened by muscle strain and thereby attributed to crosslinks that remained stable during tissue incubation in a calcium-free solution. Degradation of this signaling system could potentially contribute to urinary incontinence.
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