Reduced bladder responses to capsaicin and GSK-1016790A in retired-breeder female rats with diminished volume sensitivity

Literature documents an age related reduction of bladder sensory function. TRPV1 or TRPV4 channels have been implicated in bladder mechano-transduction. To investigate contributions of TRPV1 or TRPV4 to the age related reduction of bladder sensory function, bladder responses to capsaicin (CAP, TRPV1 agonist) and GSK1016790A (GSK, TRPV4 agonist) in retired breeder (RB, 12-15 months) and young adult (2-3 month) female rats were compared using multiple methods. Metabolic cage and continuous infusion cystometry (CMG) recordings revealed that RB rats exhibit larger bladder capacity and lower voiding frequency. RB rats also have a greater intravesical pressure threshold for micturition, however, the voiding contraction strength was equivalent to that in young rats. CAP (1μM) or GSK (20nM) administered intravesically evoked smaller changes in all CMG parameters in RB rats. In vitro, CAP (1μM) or GSK (20nM) evoked smaller enhancement of bladder strip contractions, while the muscarinic receptor agonist carbachol (...