Melatonin restores impaired contractility in aged guinea pig urinary bladder

Pedro J. Gomez-Pinilla, Maria F. Gomez, Karl Swärd, Petter Hedlund, Per Hellstrand, Pedro J. Camello, Karl Erik Andersson, María J. Pozo

Research output: Contribution to journalArticle

Abstract

Urinary bladder disturbances are frequent in the elderly population but the responsible mechanisms are poorly understood. This study evaluates the effects of aging on detrusor myogenic contractile responses and the impact of melatonin treatment. The contractility of bladder strips from adult, aged and melatonin-treated guinea pigs was evaluated by isometric tension recordings. Cytoplasmatic calcium concentration ([Ca2+]i) was estimated by epifluorescence microscopy of fura-2-loaded isolated detrusor smooth muscle cells, and the levels of protein expression and phosphorylation were quantitated by Western blotting. Aging impairs the contractile response of detrusor strips to cholinergic and purinergic agonists and to membrane depolarization. The impaired contractility correlates with increased [Ca 2+]i in response to the stimuli, suggesting a reduced Ca2+sensitivity. Indeed, the agonist-induced contractions in adult strips were sensitive to blockade with Y27362, an inhibitor of Rho kinase (ROCK) and GF109203X, an inhibitor of protein kinase C (PKC), but these inhibitors had negligible effects in aged strips. The reduced Ca2+ sensitivity in aged tissues correlated with lower levels of RhoA, ROCK, PKC and the two effectors CPI-17 and MYPT1, and with the absence of CPI-17 and MYPT1 phosphorylation in response to agonists. Interestingly, melatonin treatment restored impaired contractility via normalization of Ca2+ handling and Ca2+ sensitizations pathways. Moreover, the indoleamine restored age-induced changes in oxidative stress and mitochondrial polarity. These results suggest that melatonin might be a novel therapeutic tool to palliate aging-related urinary bladder contractile impairment.

Original languageEnglish
Pages (from-to)416-425
Number of pages10
JournalJournal of Pineal Research
Volume44
Issue number4
DOIs
Publication statusPublished - May 2008

Keywords

  • Aging
  • Calcium sensitization
  • Calcium signalling
  • Guinea pig
  • Melatonin
  • Mitochondria
  • Urinary bladder

ASJC Scopus subject areas

  • Endocrinology

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  • Cite this

    Gomez-Pinilla, P. J., Gomez, M. F., Swärd, K., Hedlund, P., Hellstrand, P., Camello, P. J., Andersson, K. E., & Pozo, M. J. (2008). Melatonin restores impaired contractility in aged guinea pig urinary bladder. Journal of Pineal Research, 44(4), 416-425. https://doi.org/10.1111/j.1600-079X.2007.00544.x