H. Henry Lai, Timothy B. Boone, Christopher P. Smith, Timothy C. Thompson, George T. Somogyi

Scott Department of Urology, Baylor College of Medicine, Houston, TX

Objective: The caveolin-1 knockout mouse has been proposed as an animal model to study impaired bladder contractility and detrusor overactivity. This study investigates the effects of aging on detrusor contraction in wildtype and caveolin-1 knockout mice.

Methods: Young (3-month-old, 3M) and old (1-year-old, 1Y) male caveolin-1 knockout mice (KO) and their age-matched male wildtype littermates (WT) were used. Longitudinal bladder strips were stimulated electrically (20 Hz) and pharmacologically using 1-10 µM carbachol (a non-subtype selective cholinergic receptor agonist), 10 µM α, β-methylene ATP (a purinergic agonist), and 100 mM potassium (a depolarizing agent). Isometric bladder strip contractions were compared between the young wildtype and knockout groups, and between the old wildtype and knockout groups.

Results: Bladder strips from 1-year-old knockout mice (KO 1Y) exhibited a 40-42% decrease in electrical neural contractions and carbachol-evoked contractions compared with 1-year-old wildtype controls (WT 1Y; p < 0.05). Even though bladder strips from 3-month-old knockout mice (KO 3M) demonstrated a smaller decrease (29-32%) in electrical neural contractions and carbachol-evoked contractions compared with age-matched controls (WT 3M), the trend did not reach statistical significance (p > 0.05). The post-junctional cholinergic pathway was specifically disrupted in caveolin-1 knockout animals since there was no difference in contractility between knockout and wildtype mice (young or old) when the bladders were stimulated by α, β-methylene ATP or potassium. The differences in cholinergic contractility between knockout and wildtype mice became significantly larger as the animals aged from 3-months-old (young bladders) to 1-year-old (aged bladders).

Conclusion: Caveolin-1 knockout mouse provides a much-needed animal model for the study of impaired detrusor contractility in the aging bladder.

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