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Age‐related changes in bladder function with altered angiotensin II receptor mechanisms in rats
Author(s) -
Mori Kenichi,
Noguchi Mitsuru,
Tobu Shohei,
Sato Fuminori,
Mimata Hiromitsu,
Tyagi Pradeep,
Chancellor Michael B.,
Yoshimura Naoki
Publication year - 2016
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.22849
Subject(s) - downregulation and upregulation , endocrinology , cystometry , medicine , angiotensin ii , receptor , renin–angiotensin system , stimulation , urinary bladder , chemistry , blood pressure , biochemistry , gene
Aims To examine alterations in expression of angiotensin II type 1 receptors (AT1R) which induce organ tissue remodeling, angiotensin II type 2 receptors (AT2R) which protect against it, and related molecules in the bladder of matured rats with bladder dysfunction. Methods Female SD rats of three different ages were used: 8 weeks old (8W; n = 5), 9 months old (9M; n = 5), and 15 months old (15M; n = 5). After cystometry, the expression levels of AT1R, connexin43 (Cx43), MAP kinase (MAPK), collagen1, AT2R, PPAR‐γ, adiponectin (Adipo), and adiponectin receptor (Adipo‐R) were investigated in the bladder. Results Pressure threshold, post‐void residual volume and the number of non‐voiding contractions were significantly increased in 15M versus 8W rats ( P < 0.01). Maximum voiding pressure was significantly decreased in 15M versus 8W rats ( P < 0.05). There was no significant difference in CMG parameters between 8W and 9M rats. In the bladder, the mRNA expression of AT1R, Cx43, MAPK, collagen 1, AT2R, PPAR‐γ, Adipo, and Adipo‐R were significantly higher in 15M than in 8W rats. The relative expression ratio of AT1R protein against AT2R protein in the mucosa and detrusor was significantly increased in 15M versus 8W rats. Conclusions These results indicate that matured rats exhibit not only bladder overactivity but also impaired voiding, which are associated with upregulation of AT1R. The upregulation of AT2R also may play a significant role in the suppressing of AT1R induced remodelling. However, because AT1R upregulation is more dominant than AT2R increases, AT2R activation may not be sufficient to suppress AT1R stimulation in matured rats. Neurourol. Urodynam. 35:908–913, 2016 . © 2015 Wiley Periodicals, Inc.