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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...

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Autores principales: de Oliveira, Amanda A., Mendoza, Valentina O., Priviero, Fernanda, Webb, R. Clinton, Nunes, Kenia P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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