Alteration in Mechanical Compliance via Mast Cell Activation in Juvenile and Adult Urinary Bladder

Abstract

Balance between bladder wall stiffness and mechanical compliance is essential to maintain normal bladder function. These biomechanical properties are directly influenced by the integrity of the extracellular matrix (ECM) and its interaction with urinary bladder smooth muscle (UBSM). While it is clear that normal storage and voiding functions differ between juveniles and adults, it is unclear if these differences are due solely to increases in bladder size. Differences in the mechanical properties of the wall may also exist and are unexplored. Changes in mechanical compliance are implicated in the pathophysiology of many lower urinary tract symptoms (LUTS) such as overactivity and fibrosis due to inflammation. Interestingly, juvenile bladders are particularly susceptible to inflammatory LUTS by various factors (e.g., early life stress) compared to their adult counterparts. We were interested in how bladders from juvenile and adult mice respond to inflammation, specifically driven by mast cell degranulation. We hypothesized that: (1) juvenile bladders are inherently more compliant than adult bladders and (2) mast cell degranulation increases mechanical compliance in both juvenile and adult mouse bladders.Whole mouse bladders from juvenile (4–5 weeks old) and adult (12–14 weeks old) C57Bl/6 male mice were dissected and mounted in a custom designed pentaplanar reflected image macroscopy (PRIM) system for simultaneous measurement of transient pressure events, intravesical pressure, bladder volume, wall stress, and wall stretch during ex vivo bladder filling. Mechanical properties of the bladder wall were measured as the relationship between mechanical stress versus stretch. Properties of the transient contractions were calculated using acquired pressure-volume curves. Measurements were performed in the absence or presence of the mast cell activator Compound 48/80 (10 μg/mL).In the absence of Compound 48/80, the average stress-stretch curves had no significant shift for adult mice compared to young mice, implying no changes in mechanical compliance. However, the mechanical stress in adult mouse bladders was higher compared to juvenile bladders, implying that adult bladders were stiffer. In presence of Compound 48/80, both age groups show similar effects. Mechanical compliance increased with a paradoxical increase in amplitude of transient contractions. Together, these data suggest that while juvenile mouse bladders are less stiff, they respond to mast cell activation in a similar manner as adult bladders. Consequently, rapid degranulation of mast cells in juvenile bladders leads to increased mechanical compliance and contractility. Thus, preventing mast cell degranulation could represent a viable target for treating LUTS in children as well as adults. R01-DK119615 (NRT) and P20-DK127554 (SR and NRT) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.