Nitric oxide‐mediated signal transmission in bladder vasculature underlies the therapeutic actions of PDE5 inhibitors in the rat
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- Hidekazu Tanaka
- Department of Cell Physiology, Graduate School of Medical Sciences Nagoya City University Nagoya Japan
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- Retsu Mitsui
- Department of Cell Physiology, Graduate School of Medical Sciences Nagoya City University Nagoya Japan
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- Mitsuhiro Oishi
- Department of Neuropsychiatry Keio University School of Medicine Tokyo Japan
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- Stefan Passlick
- Institute of Cellular Neurosciences, Medical Faculty University of Bonn Bonn Germany
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- Ronald Jabs
- Institute of Cellular Neurosciences, Medical Faculty University of Bonn Bonn Germany
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- Christian Steinhäuser
- Institute of Cellular Neurosciences, Medical Faculty University of Bonn Bonn Germany
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- Kenji F. Tanaka
- Department of Neuropsychiatry Keio University School of Medicine Tokyo Japan
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- Hikaru Hashitani
- Department of Cell Physiology, Graduate School of Medical Sciences Nagoya City University Nagoya Japan
抄録
<jats:sec><jats:title>Background and Purpose</jats:title><jats:p>While the bladder vasculature is considered as a target of PDE5 inhibitors to improve bladder storage dysfunctions, its characteristics are largely unknown. Thus, the functional and morphological properties of arteries/arterioles of the bladder focusing on the NO‐mediated signal transmission were explored.</jats:p></jats:sec><jats:sec><jats:title>Experimental Approach</jats:title><jats:p>Diameter changes in rat bladder arteries/arterioles were measured using a video‐tracking system. Intercellular Ca<jats:sup>2+</jats:sup> dynamics in pericytes or smooth muscle cells (SMCs) of suburothelial arterioles were visualised using transgenic mice expressing GCaMP6 under control of the NG2‐ or parvalbumin‐promoter. The perivascular innervation was investigated using fluorescence immunohistochemistry.</jats:p></jats:sec><jats:sec><jats:title>Key Results</jats:title><jats:p>In rat suburothelial arterioles and vesical arteries, tadalafil (100 nM) attenuated nerve‐evoked sympathetic vasoconstrictions. In both vascular segments, tadalafil‐induced inhibition of sympathetic vasoconstriction was prevented by N ω‐propyl‐<jats:sc>l</jats:sc>‐arginine hydrochloride (<jats:sc>l</jats:sc>‐NPA, 1 μM), an nNOS inhibitor or N ω‐nitro‐<jats:sc>l</jats:sc>‐arginine (<jats:sc>l</jats:sc>‐NA, 100 μM). Both vascular segments were densely innervated with nNOS‐positive nitrergic nerves in close apposition to tyrosine hydroxylase‐immunoreactive sympathetic nerves. In pericyte‐covered pre‐capillary arterioles of the mouse bladder where sympathetic nerves were absent, nerve stimulation evoked transient reductions in pericyte Ca<jats:sup>2+</jats:sup> levels that were shortened by <jats:sc>l</jats:sc>‐NPA and abolished by <jats:sc>l</jats:sc>‐NA. In SMC‐containing arterioles, tadalafil (10 nM) caused a <jats:sc>l</jats:sc>‐NPA‐sensitive suppression of sympathetic Ca<jats:sup>2+</jats:sup> transients. In mice, nitrergic perivascular nerves were distributed in the arterioles and the pre‐capillary arterioles.</jats:p></jats:sec><jats:sec><jats:title>Conclusion and Implications</jats:title><jats:p>Both nitrergic nerve and nerve‐evoked endothelial NO release appear to be involved in vasodilatory signal transmission in bladder vasculature. The NO‐mediated signal transmission is a potential target for PDE5 inhibitor therapy in bladder dysfunctions.</jats:p></jats:sec>
収録刊行物
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- British Journal of Pharmacology
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British Journal of Pharmacology 178 (5), 1073-1094, 2021-02-02
Wiley
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詳細情報 詳細情報について
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- CRID
- 1360572092657370624
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- ISSN
- 14765381
- 00071188
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- データソース種別
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- Crossref
- KAKEN