Carbachol-induced volume adaptation in mouse bladder and length adaptation via rhythmic contraction in rabbit detrusor.

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.

Length adaptation of the passive-to-active tension ratio in rabbit detrusor.

The passive and active length-tension (L-T (p) and L-T (a)) relationships in airway, vascular, and detrusor smooth muscles can adapt with length changes and/or multiple contractions. The present objectives were to (1) determine whether short-term adaptation at one muscle length shifts the entire L-T (a) curve in detrusor smooth muscle (DSM), (2) compare adaptation at shorter versus longer lengths, and (3) determine the effect of adaptation on the T (p)/T (a) ratio. Results showed that multiple KCl-induced contractions on the descending limb of the original L-T (a) curve adapted DSM strips to that length and shifted the L-T (a) curve rightward. Peak T (a) at the new length was not different from the original peak T (a), and the L-T (p) curve shifted rightward with the L-T (a) curve. Multiple contractions on the ascending limb increased both T (a) and T (p). In contrast, multiple contractions on the descending limb increased T (a) but decreased T (p). The T (p)/T (a) ratio on the original descending limb adapted from 0.540 +/- 0.084 to 0.223 +/- 0.033 (mean +/- SE, n = 7), such that it was not different from the ratio of 0.208 +/- 0.033 at the original peak T (a) length, suggesting a role of length adaptation may be to maintain a desirable T (p)/T (a) ratio as the bladder fills and voids over a broad DSM length range.

Rhythmic contraction generates adjustable passive stiffness in rabbit detrusor.

The length-tension (L-T) relationships in airway and vascular smooth muscles have been shown to adapt with length changes over time. Our prior studies have shown that the active and passive L-T relationships in rabbit detrusor smooth muscle (DSM) can adapt and that DSM exhibits adjustable passive stiffness (APS) characterized by a passive L-T curve that is a function of strain and activation history. The present study demonstrates that passive tension due to APS can represent a substantial fraction of total tension over a broad length range. Our previous studies have shown that maximal KCl-induced contractions at short muscle lengths generate APS that is revealed by increased pseudo-steady-state passive tension at longer lengths compared with previous measurements at those lengths. The objective of the present study was to determine the mechanisms involved in APS generation. Increasing the number of KCl-induced contractions or the duration of a contraction increased the amount of APS generated. Furthermore, a fraction of APS was restored in calcium-free solution and was sensitive to the general serine and threonine protein kinase inhibitor staurosporine. Most importantly, rhythmic contraction (RC) generated APS, and because RC occurs spontaneously in human bladder, a physiological role for RC was potentially identified.

Adaptation of the length-active tension relationship in rabbit detrusor.

Studies have shown that the length-tension (L-T) relationships in airway and vascular smooth muscles are dynamic and can adapt to length changes over a period of time. Our prior studies have shown that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that DSM exhibits adjustable passive stiffness (APS) characterized by a passive L-T curve that can shift along the length axis as a function of strain history and activation history. The present study demonstrates that the active L-T curve for DSM is also dynamic and that the peak active tension produced at a particular muscle length is a function of both strain and activation history. More specifically, this study reveals that the active L-T relationship, or curve, does not have a unique peak tension value with a single ascending and descending limb, but instead reveals that multiple ascending and descending limbs can be exhibited in the same DSM strip. This study also demonstrates that for DSM strips not stretched far enough to reveal a descending limb, the peak active tension produced by a maximal KCl-induced contraction at a short, passively slack muscle length of 3 mm was reduced by 58.6 +/- 4.1% (n = 15) following stretches to and contractions at threefold the original muscle length, 9 mm. Moreover, five subsequent contractions at the short muscle length displayed increasingly greater tension; active tension produced by the sixth contraction was 91.5 +/- 9.1% of that produced by the prestretch contraction at that length. Together, these findings indicate for the first time that DSM exhibits length adaptation, similar to vascular and airway smooth muscles. In addition, our findings demonstrate that preconditioning, APS and adaptation of the active L-T curve can each impact the maximum total tension observed at a particular DSM length.