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Mechanisms underlying spontaneous constrictions of postcapillary venules in the rat stomach

  • Muscle physiology
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Abstract

Postcapillary venules (PCVs) play a critical role in regulating capillary hydrostatic pressure, but their contractile mechanisms are not well understood. We examined the properties of spontaneous vasomotion and corresponding Ca2+ transients in gastric PCV. In the rat gastric submucosa, changes in PCV diameter and intracellular Ca2+ dynamics were visualised by video tracking system and fluorescent Ca2+ imaging, respectively, while PCV morphology was examined by immunohistochemistry. Stellate-shaped PCV mural cells expressing α-smooth muscle actin exhibited synchronised spontaneous Ca2+ transients to develop vasomotion which was abolished by nifedipine (1 μM), cyclopiazonic acid (10 μM), or Ca2+-activated Cl− channel inhibitors (100 μM niflumic acid, 1 μM T16Ainh-A01). A gap junction blocker (3 μM carbenoxolone) disrupted the synchrony of spontaneous Ca2+ transients amongst PCV mural cells and attenuated spontaneous vasomotion. Low chloride solution ([Cl−]0 = 12.4 mM) also disrupted the synchrony of spontaneous Ca2+ transients and abolished vasomotion. Na+-K+-Cl− co-transporter inhibitors (10 μM bumetanide, 30 μM furosemide) suppressed spontaneous Ca2+ transients and vasoconstrictions. A phosphodiesterase type 5 (PDE5) inhibitor (1 μM tadalafil) disrupted the spontaneous Ca2+ transient synchrony and abolished vasomotion in a nitric oxide (NO)-dependent manner. Thus, gastric PCVs exhibit spontaneous vasomotion, resulting from synchronised spontaneous Ca2+ transients within a network of stellate-shaped PCV mural cells. An active Cl− accumulation partly via Na+-K+-Cl− co-transport appears to be fundamental in maintaining depolarisation upon the opening of Ca2+-activated Cl− channels that triggers Ca2+ influx via voltage-dependent L-type Ca2+ channels. Basal PDE5 activity may continuously counteract vaso-relaxing effects of endothelial NO to maintain spontaneous vasomotion.

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Acknowledgments

The authors would like to thank Dr. R. J. Lang (Monash University) for his critical reading of the manuscript. The authors gratefully acknowledge that this study was partly supported by Grant-in-Aid for Young Scientists (B) (No. 26860521) from Japan Society for Promotion of the Science (JSPS) to R.M., Grant-in-Aid for Challenging Exploratory Research (No. 26670705) from JSPS to H.H. and Grant-in-Aid from The Hori Sciences and Arts Foundation to R.M.

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  1. Department of Cell Physiology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-Ku, Nagoya, 467-8601, Japan

    Retsu Mitsui & Hikaru Hashitani

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  1. Retsu Mitsui
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  2. Hikaru Hashitani
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Correspondence to Retsu Mitsui.

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The experimental protocols in the present study were approved by the Nagoya City University Medical School Experimental Animal Committee.

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Mitsui, R., Hashitani, H. Mechanisms underlying spontaneous constrictions of postcapillary venules in the rat stomach. Pflugers Arch - Eur J Physiol 468, 279–291 (2016). https://doi.org/10.1007/s00424-015-1752-y

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