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Changes of bladder activity and connexin 43-derived gap junctions after partial bladder-outlet obstruction in rats

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Abstract

Introduction

We investigated changes of vesical gap junctions in relation to changes of the micturition reflex in rats with partial bladder-outlet obstruction (BOO).

Materials and methods

A total of 66 female Sprague–Dawley rats were divided into six groups: sham operation (control); 3, 14, and 28 days after BOO; and 3 and 28 days after relief of BOO lasting for a three-day period. Under urethane anesthesia, isovolumetric cystometry was performed on each group. Expression of mRNA for the gap-junction protein connexin 43 (Cx43) in the bladder was measured in each group. Immunohistochemistry using Cx43 antibody was also performed on the bladder after BOO.

Results

The interval between bladder contractions was shorter in all of the other groups than in the control group. Expression of Cx43 mRNA was increased 3, 14, and 28 days after BOO (the peak increase was twofold), and three days after the relief of BOO, but it returned to the control level by 28 days after relief of BOO. Histologically, smooth muscle hypertrophy was detected in the bladder after BOO and punctate staining of the smooth muscle by Cx43 antibody increased after BOO.

Conclusion

These results suggest that partial BOO produces detrusor overactivity that may depend on increased intercellular communication via gap junctions in the bladder. Relief of BOO led to a decrease of Cx43 mRNA, but detrusor overactivity persisted in the chronic phase, suggesting a reversible change of vesical gap junctions and an irreversible change of bladder activity after BOO.

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References

  1. Uvelius B, Persson L, Mattiasson A (1984) Smooth muscle cell hypertrophy and hyperplasia in the rat detrusor after short-time infravesical outflow obstruction. J Urol 131:173–176

    CAS  PubMed  Google Scholar 

  2. Saito M, Longhurst PA, Tammela TL et al (1993) Effects of partial outlet obstruction of the rat urinary bladder on micturition characteristics, DNA synthesis and the contractile response to field stimulation and pharmacological agents. J Urol 150:1045–1051

    CAS  PubMed  Google Scholar 

  3. Bruzzone R, White TW, Paul DL (1996) Connections with connexins: the molecular basis of direct intercellular signaling. Eur J Biochem 238:1–27. doi:10.1111/j.1432-1033.1996.0001q.x

    Article  CAS  PubMed  Google Scholar 

  4. Christ GJ, Day NS, Day M et al (2003) Increased connexin43-mediated intercellular communication in a rat model of detrusor overactivity in vivo. Am J Physiol Regul Integr Comp Physiol 284:R1241–R1248

    CAS  PubMed  Google Scholar 

  5. Haefliger JA, Tissieres P, Tawadros T et al (2002) Connexins 43 and 26 are differentially increased after rat bladder-outlet obstruction. Exp Cell Res 274:216–225. doi:10.1006/excr.2001.5465

    Article  CAS  PubMed  Google Scholar 

  6. Neuhaus J, Weimann A, Stolzenburg JU et al (2002) Smooth muscle cells from human urinary bladder express connexin 43 in vivo and in vitro. World J Urol 20:250–254

    CAS  PubMed  Google Scholar 

  7. Neuhaus J, Pfeiffer F, Wolburg H et al (2005) Alterations in connexin expression in the bladder of patients with urge symptoms. BJU Int 96:670–676. doi:10.1111/j.1464-410X.2005.05703.x

    Article  CAS  PubMed  Google Scholar 

  8. Haferkamp A, Mundhenk J, Bastian PJ et al (2004) Increased expression of connexin 43 in the overactive neurogenic detrusor. Eur Urol 46:799–805. doi:10.1016/j.eururo.2004.08.020

    Article  CAS  PubMed  Google Scholar 

  9. Leung DS, Unsicker K, Reuss B (2002) Expression and developmental regulation of gap junction connexins cx26, cx32, cx43 and cx45 in the rat midbrain-floor. Int J Dev Neurosci 20:63–75. doi:10.1016/S0736-5748(01)00056-9

    Article  CAS  PubMed  Google Scholar 

  10. Trosko JE, Madhukar BV, Chang CC (1993) Endogenous and exogenous modulation of gap junctional intercellular communication: toxicological and pharmacological implications. Life Sci 53:1–19. doi:10.1016/0024-3205(93)90606-4

    Article  CAS  PubMed  Google Scholar 

  11. Mori K, Noguchi M, Matsuo M et al (2005) Decreased cellular membrane expression of gap junctional protein, connexin 43, in rat detrusor muscle with chronic partial bladder-outlet obstruction. Urology 65:1254–1258. doi:10.1016/j.urology.2005.01.043

    Article  PubMed  Google Scholar 

  12. Schroder A, Uvelius B, Newgreen D et al (2003) Bladder overactivity in mice after 1 week of outlet obstruction. Mainly afferent dysfunction? J Urol 170:1017–1021. doi:10.1097/01.ju.0000070926.39442.4c

    Article  PubMed  Google Scholar 

  13. Miyazato M, Sugaya K, Nishijima S et al (2008) Changes of bladder activity and glycine levels in the lumbosacral cord after partial bladder-outlet obstruction in rats. Int J Urol 15:843–847. doi:10.1111/j.1442-2042.2008.02079.x

    Article  PubMed  Google Scholar 

  14. Tanaka H, Kakizaki H, Shibata T et al (2003) Effects of chronic blockade of N-methyl-d-aspartate receptors by MK-801 on neuroplasticity of the micturition reflex pathway after partial urethral obstruction in the rat. J Urol 170:1427–1431. doi:10.1097/01.ju.0000074713.69589.4a

    Article  CAS  PubMed  Google Scholar 

  15. Knutson T, Edlund C, Fall M et al (2001) BPH with coexisting overactive bladder dysfunction—an everyday urological dilemma. Neurourol Urodyn 20:237–247. doi:10.1002/nau.1001

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research (B-14370516) from the Japan Society for the Promotion of Science, by a 2003 grant from Okinawa Medical Science Research Foundation, and by a 2005 grant from Daiwa Securities Health Foundation.

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Correspondence to Minoru Miyazato.

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Miyazato, M., Sugaya, K., Nishijima, S. et al. Changes of bladder activity and connexin 43-derived gap junctions after partial bladder-outlet obstruction in rats. Int Urol Nephrol 41, 815–821 (2009). https://doi.org/10.1007/s11255-008-9516-7

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  • DOI: https://doi.org/10.1007/s11255-008-9516-7

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