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Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70.

Age-Related Decline in Vascular Responses to Phenylephrine Is Associated with Reduced Levels of HSP70.

Authors :
de Oliveira AA
Mendoza VO
Priviero F
Webb RC
Nunes KP
Source :
Biomolecules [Biomolecules] 2022 Aug 16; Vol. 12 (8). Date of Electronic Publication: 2022 Aug 16.
Publication Year :
2022

Abstract

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 <superscript>2+</superscript> ), 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 <superscript>2+</superscript> handling as inhibition of this protein led to reduced force-displacement in response to Ca <superscript>2+</superscript> 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.

Details

Language :
English
ISSN :
2218-273X
Volume :
12
Issue :
8
Database :
MEDLINE
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
36009019
Full Text :
https://doi.org/10.3390/biom12081125