Carbachol-Induced Volume Adaptation in Mouse Bladder and Length Adaptation via Rhythmic Contraction in Rabbit Detrusor

Abstract

The length-tension (L-T) relationships in rabbit detrusor smooth muscle (DSM) are similar to those in vascular and airway smooth muscles and exhibit short-term length adaptation characterized by L-T curves that shift along the length axis as a function of activation and strain history. In contrast to skeletal muscle, the length-active tension (L-T(a)) curve for rabbit DSM strips does not have a unique peak tension value with a single ascending and descending limb. Instead, DSM can exhibit multiple ascending and descending limbs, and repeated KCl-induced contractions at a particular muscle length on an ascending or descending limb display increasingly greater tension. In the present study, mouse bladder strips with and without urothelium exhibited KCl-induced and carbachol-induced length adaptation, and the pressure-volume relationship in mouse whole bladder displayed short-term volume adaptation. Finally, prostaglandin-E(2)-induced low-level rhythmic contraction produced length adaptation in rabbit DSM strips. A likely role of length adaptation during bladder filling is to prepare DSM cells to contract efficiently over a broad range of volumes. Mammalian bladders exhibit spontaneous rhythmic contraction (SRC) during the filling phase and SRC is elevated in humans with overactive bladder (OAB). The present data identify a potential physiological role for SRC in bladder adaptation and motivate the investigation of a potential link between short-term volume adaptation and OAB with impaired contractility.

Acute length adaptation and adjustable preload in the human detrusor

“…However, with repeated contractions, T a is recovered and approaches the original T a seen at that length. This active process of length adaptation, previously identified by the authors in rDSM, has also been demonstrated in respiratory and vascular smooth muscles. Furthermore, acute length adaptation has been demonstrated as a shift of the pressure–volume curve in whole mouse bladders, which more closely models human cystometrics …”

“…Total detrusor tension can be analyzed according to its component parts: active tension (T a ) generated by DSM contraction and preload (T p ). T p can be further sub‐divided into passive tension (T pas ) derived from non‐regulatable structural components (i.e., collagen and elastin) and an adjustable preload (T ap ) that has been identified in rabbit DSM (rDSM) and other smooth muscle types . At the molecular level, T ap may result from slowly cycling actomyosin crossbridges .…”

“…The parabolic length‐active tension curve can shift to different optimum muscle lengths in response to active contractions, and this process is defined as length adaptation . The process of acute length adaptation does not occur in skeletal muscle but has been previously identified in respiratory and vascular smooth muscle, as well as rDSM . Although the function of length adaptation is unknown, this biomechanical process may help the bladder contract efficiently at a wide range of filling volumes because DSM cells are unique among muscle cells in having an approximate sevenfold operational length range.…”

Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves

“…Potential physiological roles for LARC in acute length adaptation and adjustable preload have been identified in rabbit DSM [6,21]. Length adaptation and adjustable preload have also been identified in the human detrusor, and the clinical correlate of adjustable preload, dynamic elasticity, has been identified during human urodynamics [20,22].…”

Evidence for a common mechanism for spontaneous rhythmic contraction and myogenic contraction induced by quick stretch in detrusor smooth muscle

“…) and for length adaptation (Speich et al. ). The present data are consistent with a bladder model that includes two contractile systems, one responsible for producing the voiding contraction, and another responsible for SRC, QS‐induced myogenic contraction, generation of APS (Speich et al.…”