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1 Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, USA
2 Department of Urology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA
3 Department of Anatomy and Cell Biology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA
* To whom correspondence should be addressed. E-mail: robert.moreland{at}drexel.edu.
Partial bladder outlet obstruction in the rabbit produces changes in bladder function similar to those seen clinically in patients with obstructive uropathies. Whole organ function is significantly altered as are the smooth muscle cells inside the bladder wall. This study was designed to determine if outlet obstruction alters smooth muscle function at the level of contractile filaments. Rabbit bladders were partially obstructed for two weeks. Bladder smooth muscle was detergent skinned using Triton X-100 to provide a preparation that allows control of the intracellular environment while maintaining the ability to shorten and develop force. Ca2+-force and Ca2+-myosin light chain (MLC) phosphorylation relationships and maximal velocity of shortening were determined. The Ca2+ sensitivity of force was significantly lower in animals subjected to outlet obstruction as compared to tissues from control animals. In contrast, no difference was noted in the Ca2+ sensitivity of MLC phosphorylation. Maximal levels of stress and MLC phosphorylation were similar in both animals groups. Maximal velocity of shortening was significantly slower in tissues from outlet obstructed animals at all [Ca2+] as compared to tissues from control animals. Ultrastructurally, it was found that detergent skinning had little effect on structural integrity. Moreover, the tissues from obstructed animals showed an increase in the number of sarcolemmal attachment plaque structures. We suggest that partial bladder outlet obstruction produces both deleterious, e.g., the decrease in the Ca2+ sensitivity of force, and compensatory, e.g., the increase in membrane attachment plaques, changes in bladder smooth muscle cells.
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