Impact of aging on rat urinary bladder fatigue

Purpose: Little is known about the fatigability of the urinary bladder. In these experiments, we characterized contractile and bioenergetic changes in bladder fatigue and investigated the impact of aging on these changes. Materials and Methods: Whole urinary bladders from 3-month-old (n = 17) and 24-month-old (n = 12) SD rats were isolated and individually mounted in organ baths. The bladders were electrostimulated repeatedly (50 volts, 32 Hz, 1 MS; every 2.5 minutes). The pressure generation, rate of pressure generation and the emptying ability (% volume emptied) of the isolated bladders were measured with each stimulation. After the 20th electrostimulation, the bladders were immediately stimulated with 500 mu M bethanechol. Upon completion of their series of stimulations, some of the bladders were quickly frozen in liquid nitrogen. Tissue phosphocreatine and ATP content of the frozen bladders and a group (six 3-month-old and six 24-month-old rats) of fresh bladder tissues was determined using high performance liquid chromatography (HPLC). Results: The results can be summarized as follows: (1) Pressure generation, rate of pressure generation and emptying ability were gradually reduced in both young and aged bladders as repeated stimulation proceeded. (2) The final bethanechol stimulation emptied the same intravesical volume as the 20th electrostimulation emptied (in both groups), indicating that bladder fatigue is due to a post-synaptic mechanism. (3) As compared to their own first responses, aged rats exhibited significantly greater rates of reduction in both pressure generation and emptying ability than did young rats. (4) Analysing fresh bladder tissues, the phosphocreatine and ATP concentration of the aged bladders were significantly less than those of the young bladders-13.2 +/- 2.0 and 1.2 +/- 0.3 nmol/mg, protein respectively in the aged bladders vs. 21.2 +/- 1.8 and 7.5 +/- 1.0 nmol/mg. protein respectively in the young bladders. After repeated stimulation, phosphocreatine and ATP concentration were reduced in both groups (1.4 +/- 0.3 and 0.43 +/- 0.1 nmol./mg. protein in the aged bladders, 7.5 +/- 1.4 and 4.1 +/- 0.5 nmol./mg. protein in the young bladders), with a greater degree of reduction in the aged bladders. Conclusion: These observations indicate that, in response to repeated electrostimulation, aged rat bladders became fatigued faster than young bladders. Decreased capability in energy production might be one contributing factor for faster fatiguability of the aged urinary bladders.