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Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70
Aging impairs the expression of HSP70, an emergent player in vascular biology. However, it is unknown if age-related alterations in HSP70 are linked to a decline in arterial function. In this study, we test the hypothesis that the contributions of HSP70 to vascular contraction are diminished in midd...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405859/ https://www.ncbi.nlm.nih.gov/pubmed/36009019 http://dx.doi.org/10.3390/biom12081125 |
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author | de Oliveira, Amanda A. Mendoza, Valentina O. Priviero, Fernanda Webb, R. Clinton Nunes, Kenia P. |
author_facet | de Oliveira, Amanda A. Mendoza, Valentina O. Priviero, Fernanda Webb, R. Clinton Nunes, Kenia P. |
author_sort | de Oliveira, Amanda A. |
collection | PubMed |
description | Aging impairs the expression of HSP70, an emergent player in vascular biology. However, it is unknown if age-related alterations in HSP70 are linked to a decline in arterial function. In this study, we test the hypothesis that the contributions of HSP70 to vascular contraction are diminished in middle-aged animals. We determined the basal levels of HSP70 in the aorta of young and middle-aged Sprague Dawley male rats using Western blotting. Functional studies were performed in a wire myograph system. Force development in response to phenylephrine was assessed in the presence or absence of extracellular calcium (Ca(2+)), and in aortic rings treated or non-treated with an HSP70 inhibitor. Fluorescent probes were used to evaluate vascular oxidative stress and nitric oxide levels. We report that middle-aged rats have significantly lower levels of HSP70. Blockade of HSP70 attenuated vascular phasic and tonic contraction in isolated aortas. It appears that a functional HSP70 is required for proper Ca(2+) handling as inhibition of this protein led to reduced force–displacement in response to Ca(2+) dynamics. Furthermore, middle-aged aortic rings exposed to the HSP70 inhibitor display higher reactive oxygen species levels without changes in nitric oxide. In summary, we show that middle-aged animals have lower levels of HSP70 in aortas, which associates with an age-related decline in vascular responses to α-1 adrenergic stimulation. |
format | Online Article Text |
id | pubmed-9405859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94058592022-08-26 Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70 de Oliveira, Amanda A. Mendoza, Valentina O. Priviero, Fernanda Webb, R. Clinton Nunes, Kenia P. Biomolecules Article Aging impairs the expression of HSP70, an emergent player in vascular biology. However, it is unknown if age-related alterations in HSP70 are linked to a decline in arterial function. In this study, we test the hypothesis that the contributions of HSP70 to vascular contraction are diminished in middle-aged animals. We determined the basal levels of HSP70 in the aorta of young and middle-aged Sprague Dawley male rats using Western blotting. Functional studies were performed in a wire myograph system. Force development in response to phenylephrine was assessed in the presence or absence of extracellular calcium (Ca(2+)), and in aortic rings treated or non-treated with an HSP70 inhibitor. Fluorescent probes were used to evaluate vascular oxidative stress and nitric oxide levels. We report that middle-aged rats have significantly lower levels of HSP70. Blockade of HSP70 attenuated vascular phasic and tonic contraction in isolated aortas. It appears that a functional HSP70 is required for proper Ca(2+) handling as inhibition of this protein led to reduced force–displacement in response to Ca(2+) dynamics. Furthermore, middle-aged aortic rings exposed to the HSP70 inhibitor display higher reactive oxygen species levels without changes in nitric oxide. In summary, we show that middle-aged animals have lower levels of HSP70 in aortas, which associates with an age-related decline in vascular responses to α-1 adrenergic stimulation. MDPI 2022-08-16 /pmc/articles/PMC9405859/ /pubmed/36009019 http://dx.doi.org/10.3390/biom12081125 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article de Oliveira, Amanda A. Mendoza, Valentina O. Priviero, Fernanda Webb, R. Clinton Nunes, Kenia P. Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70 |
title | Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70 |
title_full | Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70 |
title_fullStr | Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70 |
title_full_unstemmed | Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70 |
title_short | Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70 |
title_sort | age-related decline in vascular responses to phenylephrine is associated with reduced levels of hsp70 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9405859/ https://www.ncbi.nlm.nih.gov/pubmed/36009019 http://dx.doi.org/10.3390/biom12081125 |
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