In smooth muscle tissues, the relationship between muscle or cell length and active force can be modulated by altering the cell or tissue length during stimulation. Mechanisms for this mechanical plasticity were investigated by measuring muscle stiffness during isometric contractions in which contractile force was graded by changing stimulus intensity or muscle length. Stiffness was significantly higher in contracted than in resting muscles at comparable forces; however, the relationship between stiffness and force during force development was curvilinear and independent of muscle length and stimulus intensity. This suggests that muscle stiffness during force development reflects properties of cellular components other than cross bridges which contribute to the series elasticity only during activation. During the tonic phase of isometric contraction, muscle stiffness increased while force remained constant. A step decrease in the length of a contracted muscle resulted in a high level of stiffness relative to force during isometric force redevelopment following the length step. We propose that the arrangement of the cytoskeleton can adjust to changes in the conformation of resting smooth muscle cells but that the organization of the cytoskeleton becomes more fixed upon contractile activation and is modulated very slowly during a sustained contraction. This may provide a mechanism for optimizing force development to the physical conformation of the cell at the time of activation.

Reactive oxygen species alter pulmonary arterial vascular tone and cause changes in pulmonary vascular resistance. The objective of this investigation was to determine direct effects of oxygen radicals on the contractile properties of pulmonary arterial smooth muscle. Isolated pulmonary arterial rings from Sprague-Dawley rats were placed in tissue baths containing Earle's balanced salt solution (gassed with 95% O2 - 5% CO2, 37 degrees C, pH 7.4). Vessels were contracted with 80 mM KCl to establish maximum active force production (Po). All other responses were normalized as percentages of Po for comparative purposes. Reactive oxygen metabolites were generated enzymatically with either the xanthine oxidase (XO) reaction or the glucose oxidase (GO) reaction, or hydrogen peroxide (H2O2) was added directly to the muscle bath. Exposure to XO, GO, or to H2O2 resulted in a contractile response that was sustained during the 30-min exposure period. The muscle fully relaxed following removal of the reactive oxygen species. Resting tension remained unchanged throughout the experimental period, suggesting no functional change in membrane potential. The contractile response was dose dependent and was not prevented by either cyclooxygenase or lipoxygenase inhibition, or by removal of the endothelium. Pretreatment of vessels with superoxide dismutase (SOD) partially blocked the XO-induced contraction, while mannitol or deferoxamine had no effect on the response to XO. However, pretreatment with catalase (CAT) completely blocked the XO-induced contraction. These data suggest that superoxide ions and hydrogen peroxide are the major causative agents. Following O2-radical exposure, vessels showed a decrease in contractile responsiveness to 80 mM KCl (recovery response), suggesting damage to the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)

On the terminology for describing the length-force relationship and its changes in airway smooth muscle. J Appl Physiol 97: 2029 -2034, 2004; doi:10.1152/japplphysiol.00884.2004.-The observation that the length-force relationship in airway smooth muscle can be shifted along the length axis by accommodating the muscle at different lengths has stimulated great interest. In light of the recent understanding of the dynamic nature of length-force relationship, many of our concepts regarding smooth muscle mechanical properties, including the notion that the muscle possesses a unique optimal length that correlates to maximal force generation, are likely to be incorrect. To facilitate accurate and efficient communication among scientists interested in the function of airway smooth muscle, a revised and collectively accepted nomenclature describing the adaptive and dynamic nature of the lengthforce relationship will be invaluable. Setting aside the issue of underlying mechanism, the purpose of this article is to define terminology that will aid investigators in describing observed phenomena. In particular, we recommend that the term "optimal length" (or any other term implying a unique length that correlates with maximal force generation) for airway smooth muscle be avoided. Instead, the in situ length or an arbitrary but clearly defined reference length should be used. We propose the usage of "length adaptation" to describe the phenomenon whereby the length-force curve of a muscle shifts along the length axis due to accommodation of the muscle at different lengths. We also discuss frequently used terms that do not have commonly accepted definitions that should be used cautiously.smooth muscle contraction; adaptation; plasticity; cytoskeleton; contractile apparatus THE CAPACITIES OF AIRWAY SMOOTH MUSCLE to generate force and to shorten are not a unique function of muscle length. Instead, they change appreciably depending on the histories of muscle loading, length, and activation. These changes can occur over the course of days, hours, and even seconds (9, 11-14, 24, 35, 41, 44, 46). As a result, the length-force relationship of airway smooth muscle is highly mutable, and its characterization is meaningful only when the histories on which the relationship is derived are included. Length-dependent force generation in other smooth muscles is also known to be influenced by various factors (18,29,34,36,39), with the extent of influence varying from one type of smooth muscle to another. The following description of phenomena and terminology is based on and intended for airway smooth muscle, and it may or may not apply to other smooth muscle types. Current terminology that describes the length-force characteristic in airway smooth muscle is borrowed from the physiology of striated muscle but is inadequate, and in some cases ill-suited, to depict the mutable relationship in airway smooth muscle. Thus there is a need to seek a consensual agreement among scientists working in the field of airway smooth muscle biomechanics concern...

Contraction of smooth muscle in visceral organs is modified by structures external to the muscle. Within muscle tissue itself, connective tissue plays an important role in force transference among the contractile cells. Connections arranged radially can affect contractile mechanics by limiting tissue expansion at short lengths. Previous work suggests that increased stiffness at extreme shortening is due to such radial constraints. Two approaches to further study of these effects are reported. To increase radial constraints, very thin Silastic bands were placed loosely about strips of canine trachealis muscle at rest length. The strips were allowed to shorten under light afterloads, expanding until restrained by the bands. Subsequent removal of the bands allowed increased shortening, with less increase in stiffness at short lengths. Related isometric effects were observed. To reduce constraints, muscle strips were partially digested with collagenase. Compared with control conditions, this treatment permitted further shortening, with less increase in stiffness at short lengths. These results emphasize the role of extracellular structures in determining mechanical function of smooth muscle.

The dynamic stiffness of mesotubarium smooth muscle from nonpregnant adult rabbits was measured continuously during isometric contraction by applying small (0.5 percent of the muscle length) sinusoidal length perturbations and measuring the amplitude and phase of the resulting tension perturbations. Stiffness during contraction was directly proportional to muscle tension; during relaxation stiffness at all tensions was significantly increased as compared to the values encountered during the rise of tension. Peak isometric tension and dynamic stiffness (determined at a common tension level) both decreased at shorter muscle lengths; the relative falloff in stiffness was significantly less than the tension decrease. Varying levels of muscle activation (obtained by changing stimulus strength and by applying quick releases to active muscle) had little effect on the measured elastic modulus. Comparisons of these results with published data on single-cell contractile properties imply a cellular locus for a portion of the measured stiffness.