The aging effects on phenylephrine-induced relaxation of bladder in mice

Abstract

Objective: We have demonstrated that phenylephrine (PE) activates the capsaicin-sensitive nerves, and then activates capsaicin-sensitive nerves to release an unknown substance that facilitates the release of norepinephrine (NE) from adrenergic nerves. Subsequently, NE stimulates β-ARs in the detrusor muscle in mice, leading to neurogenic relaxation of the urinary bladder (UB).

Materials and methods: We examined if there existed sensory-motor dysfunction in UB of aging mice. To investigate the change of PE-induced detrusor relaxation in aging male-C57BL/6 mice (12- vs. 24-month-old mice), UB strips from mice were isolated, cut into strips, and mounted in the organ bath.

Results: The UB strip contractility responding to various agents was estimated using tissue bath wire myography. Acetylcholine (ACh) and KCl-induced UB strips contraction was not significantly different between 24- and 12-month mice. NE-induced UB strips relaxation was significantly lower in 24-month than 12-month mice. Denuded bladder strips showed similar decreased relaxation response to NE. This NE-induced relaxation was inhibited by silodosin and lidocaine. PE did not induce contraction in UB strips of aging mice. In contrast, PE-induced relaxation was weaker in 24-month than 12-month mice.

Conclusion: Our results suggested that the PE-induced relaxation was age related. Aging seemed to lead the sensory-motor dysfunction. More animal and human studies are required to prove this concept and its clinical usefulness in the future.

Keywords: Adrenergic receptor; Aging; Bladder; Lower urinary tract dysfunction; Sensory-motor interaction.

Figure 1

Effects of age on KCl- and acetylcholine-induced contraction. The KCl (70 mM)-induced maximal contraction in 12- and 24-month mice were not significantly different (n = 11-8, P > 0.05, a). A representative tracing shows acetylcholine (acetylcholine, 0.001–10 μM)-induced contraction in 12-month (upper panel, b), and 24-month (lower panel, b) mice, in urothelium intact urinary bladder in the absence of active muscle tone. This constriction was not different between 12- and 24-month bladder strips (n = 11 ~ 6, P > 0.05, c). Values are mean ± standard error mean, n = number of experiments. W: Wash

Figure 2

Effects of age on norepinephrine-induced relaxation. Norepinephrine (NE, 0.001–10 μM)-induced relaxation in with (a) and without (b) mucosa bladder strips of aging mice (12 and 24 months, n = 6), in the presence of active muscle tone induced by acetylcholine (10 μM). The NE-induced relaxation was significantly greater in 12-month than that in 24-month mice urinary bladder (n = 6, P < 0.05). This NE (0.001–10 μM)-induced relaxation was significantly inhibited by silodosin (10 μM, n = 5, c), and lidocaine (0.1 mM, n = 5, P < 0.05, c) in 12-month mice with urothelium. Values are mean ± standard error mean. n = number of experiments. W: wash. Asterisk indicates a significant difference in Bonferroni posttests following ANOVA (*P < 0.05)

Figure 3

Effects of age on phenylephrine-induced relaxation. The phenylephrine (PE, 0.001 ~ 10 μM)-induced relaxation was significantly greater in 12-month (a, n = 6) mice than that in 24-month (a, n = 6) mice urinary bladder (P < 0.05). A similar result was found in without mucosa UB of aging mice (b, n = 5, P < 0.05). Values are mean ± standard error mean. n = number of experiments. Asterisk indicates a significant difference in Bonferroni posttests following ANOVA (*P < 0.05)