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The effect of hypercholesterolemia on carbachol-induced contractions of the detrusor smooth muscle in rats: increased role of L-type Ca2+ channels

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Abstract

To investigate a possible relation between hypercholesterolemia and detrusor smooth muscle function, we studied the contractile response to potassium challenge, carbachol (CCh), and the components of CCh-induced contractile mechanism in high-cholesterol diet-fed rats. Adult male Sprague–Dawley rats were fed with standard (control group, N = 17) or 4 % cholesterol diet (hypercholesterolemia group (HC), N = 16) for 4 weeks. Spontaneous contractions of detrusor muscle strips and their responses to potassium chloride (KCl) or cumulative dose–contraction curves to CCh were recorded. The effects of muscarinic receptor antagonists (methoctramin and/or 4-diphenylacetoxy-N-methylpiperidine), L-type Ca+2 channel blocker (nifedipine), and/or rho-kinase inhibitor Y-27632 were investigated. Blood cholesterol level was increased in the HC group with no sign of atherosclerosis. The KCl-induced detrusor smooth muscle contractions were higher in HC, whereas spontaneous and CCh-induced responses were similar in both groups. Preincubation with receptor antagonist for M3 but not for M2 attenuated contraction significantly, shifting the dose–response curve to the right. This response was similar in both groups. Among two effector mechanisms of M3-mediated detrusor smooth muscle contraction, rho-kinase pathway was not affected by hypercholesterolemia, whereas blockade of L-type Ca+2 channels potently reduced contractions. The results of this study point out a relation between hypercholesterolemia and contractile mechanism of detrusor smooth muscle likely to change urinary bladder function, via altering L-type Ca+2 channels. Taken together with escalating incidence of hypercholesterolemia and lower urinary tract symptoms, it is a field which deserves to be investigated further.

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Acknowledgments

This study was supported by the Hacettepe University Research Foundation (HUBAB; 01-G-019 and 07-D09-101-03) and The Scientific and Technological Research Council of Turkey (TUBITAK: 106-S-244). The authors would like to thank Gülsen Öner, Ph.D., Professor of Physiology for her critical and initiative contribution in this study and Rıfkı Finci, MD, Professor of Pathology for histopathological evaluation of aortic arch.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Hacettepe University, 39, Sihhiye, 06100, Ankara, Turkey

    Zeynep Dicle Balkanci, Bilge Pehlivanoğlu, Sibel Bayrak, İsmail Karabulut, Serkan Karaismailoğlu & Ayşen Erdem

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  1. Zeynep Dicle Balkanci
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  2. Bilge Pehlivanoğlu
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Correspondence to Bilge Pehlivanoğlu.

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Balkanci, Z.D., Pehlivanoğlu, B., Bayrak, S. et al. The effect of hypercholesterolemia on carbachol-induced contractions of the detrusor smooth muscle in rats: increased role of L-type Ca2+ channels. Naunyn-Schmiedeberg's Arch Pharmacol 385, 1141–1148 (2012). https://doi.org/10.1007/s00210-012-0784-5

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