Relationship between connexin43-derived gap junction proteins in the bladder and age-related detrusor underactivity in rats
Relationship between connexin43-derived gap junction proteins in the bladder and age-related detrusor underactivity in rats
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DOI：
10.1016/j.lfs.2014.08.009
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发表时间：
2014-10-22
期刊：
影响因子：
6.1
通讯作者：
Saito, Seiichi
中科院分区：
文献类型：
--
作者：
Oshiro, Takuma;Miyazato, Minoru;Saito, Seiichi
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Aims: To confirm the mechanisms of age-associated detrusor underactivity (DU), we examined the differences in bladder activity and connexin-43 (Cx43)-derived gap junctions in the bladders of young and old rats.Main methods: Female Sprague-Dawley rats aged 3 months (young) and 12 months (old) were used. Continuous cystometry was performed under urethane anesthesia in both ages of rats. In addition, isovolumetric cystometry was performed in young rats during the intravesical application of carbenoxolone, a gap junction blocker, to confirm the role of gap junction proteins in the bladder. Western blotting analyses were performed to assess Cx43 protein expression in the bladders of both groups of rats. Bladders were also analyzed using Masson's trichrome staining and immunostaining for Cx43.Key findings: Cystometric evaluations revealed that compared with young rats, bladder contractility was reduced by 27% and residual urine volume was significantly increased in old rats. However, the intercontraction intervals did not differ between the two groups. Under isovolumetric conditions, bladder contraction was suppressed after the intravesical application of carbenoxolone. In the bladders of old rats, increase of smooth muscle cell hypertrophy and fibrous tissue was observed compared with young rats. In association with these findings, immunostaining for smooth muscle Cx43 and its protein level were decreased by 28% compared with young rats.Significance: These results suggest that age-related DU might be caused by the downregulation of gap junctional intercellular communication in the bladder. Consequently, the normal signals that contribute to voiding function might not be transported between detrusor muscles. (C) 2014 Elsevier Inc. All rights reserved.