Effects of estrogen on age-related changes in muscarinic responsiveness of the urinary bladder and lumbosacral dorsal root ganglion cells in female rats.

ABSTRACT

The aim of this study was to investigate estrogen's effect on age-related changes in bladder function. Female Wistar rats were divided into three groups that included young rats (3-month-old) (YR), old rats (13-month-old) (OR), and old rats given subcutaneous treatments of estradiol for 6 weeks (OR + E). The groups were evaluated for (i) micturition behavior, (ii) changes of detrusor contractility and frequency of detrusor contraction in response to muscarinic stimulation in cystometrograms, (iii) messenger RNA (mRNA) expression of the muscarinic receptor subtype in the detrusor muscle, as measured by real-time polymerase chain reaction, and (iv) the immunoreactivity of P2X(3), CGRP, and substance P in the lumbosacral dorsal root ganglia. There were no significant changes for the average micturition volumes or micturition frequencies seen among the three groups. Moreover, there were no significant differences in the proportion of the immunoreactivities of P2X(3), CGRP, and substance P in afferent neurons among these three groups. However, an intravenous administration of muscarine significantly increased the frequency during continuous cystometrograms in the OR and OR + E groups. In these groups, there was a significant increase in the expression of the M(2) receptor mRNAs as compared to YR. It appears that the up-regulation of the M(2) receptor may lead to a decreased intercontraction interval by muscarinic stimuli. OR + E rats showed a significant increase in bladder weight as compared to the OR group. The muscarine-stimulated contractility of the detrusor in the cystometrogram also exhibited a significant increase in the OR + E group as compared to the OR group, which resulted from estrogen-induced functional hypertrophy of the detrusor muscle. These findings suggest that as little as 6 weeks of estrogen treatment is capable of improving the detrusor contractility, although the treatment contributes little to the storage phase of the micturition cycle.