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Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure
Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension i...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281320/ https://www.ncbi.nlm.nih.gov/pubmed/30511640 http://dx.doi.org/10.7554/eLife.42628 |
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author | Bulley, Simon Fernández-Peña, Carlos Hasan, Raquibul Leo, M Dennis Muralidharan, Padmapriya Mackay, Charles E Evanson, Kirk W Moreira-Junior, Luiz Mata-Daboin, Alejandro Burris, Sarah K Wang, Qian Kuruvilla, Korah P Jaggar, Jonathan H |
author_facet | Bulley, Simon Fernández-Peña, Carlos Hasan, Raquibul Leo, M Dennis Muralidharan, Padmapriya Mackay, Charles E Evanson, Kirk W Moreira-Junior, Luiz Mata-Daboin, Alejandro Burris, Sarah K Wang, Qian Kuruvilla, Korah P Jaggar, Jonathan H |
author_sort | Bulley, Simon |
collection | PubMed |
description | Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α(1)-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na(+) current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure. |
format | Online Article Text |
id | pubmed-6281320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-62813202018-12-07 Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure Bulley, Simon Fernández-Peña, Carlos Hasan, Raquibul Leo, M Dennis Muralidharan, Padmapriya Mackay, Charles E Evanson, Kirk W Moreira-Junior, Luiz Mata-Daboin, Alejandro Burris, Sarah K Wang, Qian Kuruvilla, Korah P Jaggar, Jonathan H eLife Neuroscience Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α(1)-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na(+) current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure. eLife Sciences Publications, Ltd 2018-12-04 /pmc/articles/PMC6281320/ /pubmed/30511640 http://dx.doi.org/10.7554/eLife.42628 Text en © 2018, Bulley et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Bulley, Simon Fernández-Peña, Carlos Hasan, Raquibul Leo, M Dennis Muralidharan, Padmapriya Mackay, Charles E Evanson, Kirk W Moreira-Junior, Luiz Mata-Daboin, Alejandro Burris, Sarah K Wang, Qian Kuruvilla, Korah P Jaggar, Jonathan H Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure |
title | Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure |
title_full | Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure |
title_fullStr | Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure |
title_full_unstemmed | Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure |
title_short | Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure |
title_sort | arterial smooth muscle cell pkd2 (trpp1) channels regulate systemic blood pressure |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281320/ https://www.ncbi.nlm.nih.gov/pubmed/30511640 http://dx.doi.org/10.7554/eLife.42628 |
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