EFFECT OF PHYSICAL FORCES ON BLADDER SMOOTH-MUSCLE AND UROTHELIUM

Abnormalities in bladder physiology may be due to obstruction (pressur e) and/or neurological impairment. Clinically they can result in an in crease in connective tissue and a decrease in bladder compliance. To s tudy the effects of physical forces on the bladder without the influen ce of the nerves we developed a cellular model system by isolating the 2 major cell types in the bladder: smooth muscle and urothelial cells . Extracellular matrix protein biosynthesis by these 2 cell types in v itro has been characterized by metabolic labeling of proteins with [C- 14] radiolabeled proline and analysis by gel electrophoresis. These st udies demonstrate that fetal bovine bladder smooth muscle and urotheli al cells synthesize fibronectin and types I and III interstitial colla gen. Since bladder cells exist in an active physical environment, we h ave attempted to simulate this at the cellular level. Using a device d eveloped in our laboratory, we applied a precise and reproducible mech anical strain (physical force) to these 2 cell types. By enzyme linked immunosorbent assay we quantitated collagen types I and III and fibro nectin synthesized by fetal bovine bladder smooth muscle and urothelia l cells undergoing mechanical strain (4.9%). These cells were compared to unstrained control cells that were exposed to the same experimenta l conditions. For bladder smooth muscle cells we found a significant i ncrease in collagen type III and fibronectin synthesis when compared t o unstrained cells. In contrast, collagen type I synthesis decreased w ith mechanical strain. For bladder urothelial cells we found an increa se in collagen type I and fibronectin while collagen type III remained unchanged. These studies demonstrate that extracellular matrix synthe sis by urothelial and smooth muscle cells can be modulated by stretch (strain) in the absence of neurological input. It is likely that bladd er function may be impaired as a result of abnormal synthesis of conne ctive tissue.