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1 Department of Internal Medicine, Sanof-Synthelabo, Rueil-Malmaison, France
2 Unite 430, INSERM, Paris, France
* To whom correspondence should be addressed. E-mail: philippe.lluel{at}sanofi-synthelabo.com.
The micturition profile in conscious animals and the urethro-vesical coordination in anesthetized conditions were investigated in 6- and 24-mo-old male Sprague Dawley rats. The in vitro pharmacological response to KCl, electrical field stimulation (EFS) carbachol, phenylephrine and isoprenaline were determined in the isolated bladder body, the bladder neck and urethra. A morphometrical and immunohistological study has been included. During conscious cystomanometry, 63% of the aging rats but only 25% of the adult rats showed spontaneous contractions during the bladder filling phase. In conscious aging rats, basal pressure, threshold pressure and micturition pressure were also significantly increased. In anesthetized aging rats, a decrease in resting urethral pressure at micturition threshold and the occurrence of a significant delay in urethral relaxation during micturition were associated with an increased residual volume. In all isolated tissues, contractile response to KCl were not modified with aging whereas age-related decreases in maximal responses to carbachol in the bladder body and to phenylephrine and carbachol in the urethra were observed. In the bladder neck only we found a significant decrease in the amplitude of neurogenic contractions associated with fibrosis but without decrease in nerve density. These experiments show significant modifications in the voiding pattern of aging rats associated with urethral dysfunction and with regionally specific pharmacological and structural changes of the urinary tract. We propose that aging in rats is characterized by an impairment of the urethro-vesical coordination leading to bladder dysfunctions similar to those induced by bladder outlet obstruction.
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