Identification of potential therapeutic targets in hypertension-associated bladder dysfunction

Makoto Yono, Masaki Yoshida, Yasuhiro Yamamoto, Aya Imanishi, Atsushi Fukagawa, Jamshid Latifpour, Masatoshi Eto

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: To investigate differential gene expression profiles in the bladder of spontaneously hypertensive rat (SHR), as the underlying mechanisms involved in hypertension-associated bladder dysfunction remain to be clarified. Materials and methods: SHR and normotensive Wistar-Kyoto (WKY) rats were distributed initially in three groups: group 1 received doxazosin (30 mg/kg/day); group 2 received nifedipine (30 mg/kg/day); and group 3 received the vehicle orally for 4 weeks. The alterations in gene expression levels of candidate genes identified by microarray analysis with potential biological relevance were verified by real-time reverse transcription-polymerase chain reaction (RT-PCR). Results: Voiding frequency was significantly higher, and mean voided volume was significantly lower in untreated SHRs than untreated WKY rats. Microarray analysis revealed that 25 of the differentially expressed genes in untreated SHRs compared to untreated WKY rats were related to Gs, Gi, Gq and G12/13 signalling, calcium handling, ion transport and smooth muscle-related genes. Furthermore, RT-PCR data, in accord with the microarray analysis, indicated that untreated SHRs had lower mRNA expression levels of Adcy2, Adcy3, Rgs2, Rgs3, Rgs4 and Arhgdia, and higher mRNA expression levels of Arhgef1, Arhgef11, Arhgef12, Geft, Rock1 and Rock2 than untreated WKY rats. The differential alterations in the micturition patterns and in the expression of several genes related to G-protein signalling pathway observed in SHRs were attenuated by treatment with doxazosin, but not nifedipine. Conclusion: Our data suggest that differential alterations in the expression of several genes related to Gs, Gq and G 12/13 signalling pathways in the SHR bladder might be important in hypertension-associated bladder dysfunction.

Original languageEnglish
Pages (from-to)877-883
Number of pages7
JournalBJU International
Volume105
Issue number6
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

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Inbred WKY Rats
Urinary Bladder
Inbred SHR Rats
Microarray Analysis
Doxazosin
Hypertension
Nifedipine
Gene Expression
Reverse Transcription
Genes
Polymerase Chain Reaction
Messenger RNA
Calcium Signaling
Urination
Ion Transport
Therapeutics
Transcriptome
GTP-Binding Proteins
Smooth Muscle

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Identification of potential therapeutic targets in hypertension-associated bladder dysfunction. / Yono, Makoto; Yoshida, Masaki; Yamamoto, Yasuhiro; Imanishi, Aya; Fukagawa, Atsushi; Latifpour, Jamshid; Eto, Masatoshi.

In: BJU International, Vol. 105, No. 6, 03.2010, p. 877-883.

Research output: Contribution to journalArticle

Yono, M, Yoshida, M, Yamamoto, Y, Imanishi, A, Fukagawa, A, Latifpour, J & Eto, M 2010, 'Identification of potential therapeutic targets in hypertension-associated bladder dysfunction', BJU International, vol. 105, no. 6, pp. 877-883. https://doi.org/10.1111/j.1464-410X.2009.08809.x
Yono, Makoto ; Yoshida, Masaki ; Yamamoto, Yasuhiro ; Imanishi, Aya ; Fukagawa, Atsushi ; Latifpour, Jamshid ; Eto, Masatoshi. / Identification of potential therapeutic targets in hypertension-associated bladder dysfunction. In: BJU International. 2010 ; Vol. 105, No. 6. pp. 877-883.
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