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 the se changes. Materials and Methods: Whole urinary bladders from 3-month -old (n = 17) and 24-month-old (n = 12) SD rats were isolated and indi vidually mounted in organ baths. The bladders were electrostimulated r epeatedly (50 volts, 32 Hz, 1 MS; every 2.5 minutes). The pressure gen eration, rate of pressure generation and the emptying ability (% volum e emptied) of the isolated bladders were measured with each stimulatio n. After the 20th electrostimulation, the bladders were immediately st imulated with 500 mu M bethanechol. Upon completion of their series of stimulations, some of the bladders were quickly frozen in liquid nitr ogen. Tissue phosphocreatine and ATP content of the frozen bladders an d 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 gra dually reduced in both young and aged bladders as repeated stimulation proceeded. (2) The final bethanechol stimulation emptied the same int ravesical volume as the 20th electrostimulation emptied (in both group s), indicating that bladder fatigue is due to a post-synaptic mechanis m. (3) As compared to their own first responses, aged rats exhibited s ignificantly greater rates of reduction in both pressure generation an d emptying ability than did young rats. (4) Analysing fresh bladder ti ssues, 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 you ng bladders. After repeated stimulation, phosphocreatine and ATP conce ntration were reduced in both groups (1.4 +/- 0.3 and 0.43 +/- 0.1 nmo l./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 reductio n in the aged bladders. Conclusion: These observations indicate that, in response to repeated electrostimulation, aged rat bladders became f atigued faster than young bladders. Decreased capability in energy pro duction might be one contributing factor for faster fatiguability of t he aged urinary bladders.