Rho kinase and Na+ /H+ exchanger mediate endothelin-1-induced pulmonary arterial smooth muscle cell proliferation and migration

Physiological Reports
John HuetschLarissa A Shimoda

Abstract

Excessive production of endothelin-1 (ET-1) has been observed in almost all forms of pulmonary hypertension. ET-1, a highly potent vasoconstrictor, can also potentiate pulmonary arterial smooth muscle cell (PASMC) growth and migration, both of which contribute to the vascular remodeling that occurs during the development of pulmonary hypertension. Increasing evidence indicates that alkalinization of intracellular pH (pHi ), typically due to activation of Na+ /H+ exchange (NHE), is associated with enhanced PASMC proliferation and migration. We recently demonstrated that application of exogenous ET-1 increased NHE activity in murine PASMCs via a mechanism requiring Rho kinase (ROCK). However, whether ROCK and/or increased NHE activity mediate ET-1-induced migration and proliferation in PASMCs remains unknown. In this study, we used fluorescent microscopy in transiently cultured PASMCs from distal pulmonary arteries of the rat and the pH-sensitive dye, BCECF-AM, to measure changes in resting pHi and NHE activity induced by exposure to exogenous ET-1 (10-8  mol/L) for 24 h. Cell migration and proliferation in response to ET-1 were also measured using Transwell assays and BrdU incorporation, respectively. We found that application o...Continue Reading

References

Dec 1, 1992·The American Journal of Physiology·K JanakideviA B Malik
Dec 1, 1991·American Journal of Respiratory Cell and Molecular Biology·D A QuinnC R Scheid
Mar 11, 1991·The American Journal of Physiology·A BobikS Grinpukel
Sep 1, 1990·Experimental Lung Research·J Y WestcottR F O'Brien
Jun 17, 1993·The New England Journal of Medicine·A GiaidD J Stewart
Feb 1, 1996·American Journal of Respiratory Cell and Molecular Biology·D A QuinnC A Hales
May 1, 1998·American Journal of Respiratory and Critical Care Medicine·D A QuinnC A Hales
Aug 26, 1998·The EMBO Journal·T TominagaD L Barber
Feb 13, 2001·American Journal of Physiology. Lung Cellular and Molecular Physiology·J A MaddenJ G Kleinman
Jul 2, 2003·European Journal of Medicinal Chemistry·B MasereelD Laeckmann
Sep 10, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Tetsutaro NagaokaMasahiko Oka
Jun 21, 2005·American Journal of Physiology. Lung Cellular and Molecular Physiology·Eon J RiosLarissa A Shimoda
Jun 13, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Larissa A ShimodaGregg L Semenza
Dec 11, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·E Miles WhitmanLarissa A Shimoda
Mar 4, 2008·American Journal of Respiratory and Critical Care Medicine·Lunyin YuCharles A Hales
Mar 31, 2010·The European Respiratory Journal·K T B MouchaersW J van der Laarse
Aug 21, 2010·Canadian Journal of Physiology and Pharmacology·David F Meoli, R James White
Apr 2, 2011·American Journal of Respiratory Cell and Molecular Biology·Lunyin Yu, Charles A Hales
Mar 6, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Trevor LukeLarissa A Shimoda
Dec 4, 2012·Free Radical Biology & Medicine·Olga RafikovaStevan P Tofovic
Jan 22, 2013·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Larissa A Shimoda, Steven S Laurie
Feb 19, 2013·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sarah PisarcikLarissa A Shimoda
Dec 21, 2013·Journal of the American College of Cardiology·Nazzareno GalièAnne Keogh
Jun 13, 2015·Pulmonary Circulation·John Huetsch, Larissa A Shimoda

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Citations

Sep 12, 2019·Physiological Reviews·S F Pedersen, L Counillon
Aug 28, 2020·International Journal of Hypertension·Shixin HeZhenfei Fang
Jul 25, 2019·Annals of Vascular Surgery·Luca RoncatiGraziana Gallo

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