It is well known that the overlap between the thick and thin filaments in striated muscle is responsible for the single active length-tension (L-T) curve. With the lack of visible striations, a sarcomeric unit has not been identified in smooth muscle. Though once thought to function like striated muscle via a sliding filament mechanism of contraction, recent studies on length-adaptation (L-adaptation) in airway smooth muscle (ASM), in which increased tension is generated with repeated contraction, have led to the hypothesis of a dynamic L-T curve in smooth muscle. Although more established in ASM, two studies have shown L-adaptation in vascular smooth muscle (VSM). In this project, the L-T curve over a 3-fold length range in rabbit femoral artery was investigated and the presence of more than one active and passive L-T curve was identified. The third of three repeated KCL-induced contractions at a single, shortened length resulted in L-adaptation in which the phasic and tonic phases of contraction demonstrated a 10-15% increase in active tension (Ta) relative to the first contraction. Experiments investigating possible mechanism(s) responsible for this phenomenon demonstrated that neither an increase in [Ca2+]i nor an increase in MLC20 phosphorylation was responsible for the increased tension. However, actin polymerization did appear to play a role in the L-adaptation of both phases of contraction. Thus directions for future research could include further study of actin polymerization in VSM that contributes to L-adaptation and may ultimately result in artery remodeling.

Overactive bladder (OAB), involuntary contractions during bladder filling, is a common condition affecting 17% of the adult population worldwide, and in the U.S. ranks ahead of diabetes in a list of the 10 most common chronic disorders (Mullins 2009). Mechanical mechanisms contributing to OAB are not completely understood and because of the unique function and broad volume range of the bladder, there may be mechanical characteristics that distinguish detrusor smooth muscle (DSM) in bladder from other smooth muscles. Recent studies have shown that the length-passive tension curve in DSM exhibits adjustable passive stiffness (APS) characterized by a passive curve that can be shifted along the length axis as a function of strain history and activation history; however, the mechanical mechanisms responsible for APS remain to be determined. Also, whether DSM exhibits a dynamic length-active tension relationship, as has been identified in airway and vascular smooth muscles, has not been investigated. This dissertation focused on both the passive and active length-tension relationships in DSM and the mechanical mechanisms responsible for these relationships. The first objective was to study the impact of APS on the length-total tension relationship and identify the mechanical mechanisms responsible for generating APS. The second objective was to determine whether the length-active tension relationship is adaptive and identify specific mechanical mechanisms contributing to any adaptive behavior. The results showed that a shift in the length-passive tension curve due to APS corresponded with a shift in the length-total tension curve in DSM, and that APS was 27.0±8.4% of active tension at the optimum length for active tension generation. Most importantly, low-grade rhythmic contraction (RC), which can occur spontaneously in rabbit and human bladders, regenerated APS. Results also showed that the length-active tension curve shifted due to stretch to and then activation at long lengths, as well as either multiple KCl-induced maximal contractions or RC. Thus, DSM exhibits length adaptation, and RC may contribute to both APS and length adaptation. Because increased RC has been correlated with OAB, understanding RC, APS and length-adaptation in bladder may enable the identification of specific targets for new treatments for OAB.