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The depressor response to intracerebroventricular hypotonic saline is sensitive to TRPV4 antagonist RN1734

Several reports have shown that the periventricular region of the brain, including the paraventricular nucleus (PVN), is critical to sensing and responding to changes in plasma osmolality. Further studies also implicate the transient receptor potential ion channel, type V4 (TRPV4) channel in this ho...

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Autores principales: Feetham, Claire H., Nunn, Nicolas, Barrett-Jolley, Richard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407506/
https://www.ncbi.nlm.nih.gov/pubmed/25954200
http://dx.doi.org/10.3389/fphar.2015.00083
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author Feetham, Claire H.
Nunn, Nicolas
Barrett-Jolley, Richard
author_facet Feetham, Claire H.
Nunn, Nicolas
Barrett-Jolley, Richard
author_sort Feetham, Claire H.
collection PubMed
description Several reports have shown that the periventricular region of the brain, including the paraventricular nucleus (PVN), is critical to sensing and responding to changes in plasma osmolality. Further studies also implicate the transient receptor potential ion channel, type V4 (TRPV4) channel in this homeostatic behavior. In previous work we have shown that TRPV4 ion channels couple to calcium-activated potassium channels in the PVN to decrease action potential firing frequency in response to hypotonicity. In the present study we investigated whether, similarly, intracerebroventricular (ICV) application of hypotonic solutions modulated cardiovascular parameters, and if so whether this was sensitive to a TRPV4 channel inhibitor. We found that ICV injection of 270 mOsmol artificial cerebrospinal fluid (ACSF) decreased mean blood pressure, but not heart rate, compared to naïve mice or mice injected with 300 mOsmol ACSF. This effect was abolished by treatment with the TRPV4 inhibitor RN1734. These data suggest that periventricular targets within the brain are capable of generating depressor action in response to TRPV4 ion channel activation. Potentially, in the future, the TRPV4 channel, or the TRPV4–K(Ca) coupling mechanism, may serve as a therapeutic target for treatment of cardiovascular disease.
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spelling pubmed-44075062015-05-07 The depressor response to intracerebroventricular hypotonic saline is sensitive to TRPV4 antagonist RN1734 Feetham, Claire H. Nunn, Nicolas Barrett-Jolley, Richard Front Pharmacol Pharmacology Several reports have shown that the periventricular region of the brain, including the paraventricular nucleus (PVN), is critical to sensing and responding to changes in plasma osmolality. Further studies also implicate the transient receptor potential ion channel, type V4 (TRPV4) channel in this homeostatic behavior. In previous work we have shown that TRPV4 ion channels couple to calcium-activated potassium channels in the PVN to decrease action potential firing frequency in response to hypotonicity. In the present study we investigated whether, similarly, intracerebroventricular (ICV) application of hypotonic solutions modulated cardiovascular parameters, and if so whether this was sensitive to a TRPV4 channel inhibitor. We found that ICV injection of 270 mOsmol artificial cerebrospinal fluid (ACSF) decreased mean blood pressure, but not heart rate, compared to naïve mice or mice injected with 300 mOsmol ACSF. This effect was abolished by treatment with the TRPV4 inhibitor RN1734. These data suggest that periventricular targets within the brain are capable of generating depressor action in response to TRPV4 ion channel activation. Potentially, in the future, the TRPV4 channel, or the TRPV4–K(Ca) coupling mechanism, may serve as a therapeutic target for treatment of cardiovascular disease. Frontiers Media S.A. 2015-04-23 /pmc/articles/PMC4407506/ /pubmed/25954200 http://dx.doi.org/10.3389/fphar.2015.00083 Text en Copyright © 2015 Feetham, Nunn and Barrett-Jolley. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Feetham, Claire H.
Nunn, Nicolas
Barrett-Jolley, Richard
The depressor response to intracerebroventricular hypotonic saline is sensitive to TRPV4 antagonist RN1734
title The depressor response to intracerebroventricular hypotonic saline is sensitive to TRPV4 antagonist RN1734
title_full The depressor response to intracerebroventricular hypotonic saline is sensitive to TRPV4 antagonist RN1734
title_fullStr The depressor response to intracerebroventricular hypotonic saline is sensitive to TRPV4 antagonist RN1734
title_full_unstemmed The depressor response to intracerebroventricular hypotonic saline is sensitive to TRPV4 antagonist RN1734
title_short The depressor response to intracerebroventricular hypotonic saline is sensitive to TRPV4 antagonist RN1734
title_sort depressor response to intracerebroventricular hypotonic saline is sensitive to trpv4 antagonist rn1734
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407506/
https://www.ncbi.nlm.nih.gov/pubmed/25954200
http://dx.doi.org/10.3389/fphar.2015.00083
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