Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles

Amanda J. Leblanc, Bei Chen, Patrick J. Dougherty, Rafael A. Reyes, Robert D. Shipley, Donna H. Korzick, Judy M. Muller-Delp

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Objective: The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age-induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex-specific. Methods: Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor-specific signaling. Results: In intact arterioles from males, ET-induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age-related differences in responses to ET; however, denudation of arterioles from both sexes revealed age-related differences in ETa-mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age-related changes in ET signaling occur downstream of ET receptors. Conclusions: Thus, aging-induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex-specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.

Original languageEnglish (US)
Pages (from-to)365-376
Number of pages12
JournalMicrocirculation
Volume20
Issue number5
DOIs
StatePublished - Jul 1 2013

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Endothelins
Arterioles
Vasoconstriction
Vasoconstrictor Agents
Cardiovascular Diseases
Endothelin Receptors
Proteins
Sex Characteristics
Heart Diseases

All Science Journal Classification (ASJC) codes

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Leblanc, A. J., Chen, B., Dougherty, P. J., Reyes, R. A., Shipley, R. D., Korzick, D. H., & Muller-Delp, J. M. (2013). Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles. Microcirculation, 20(5), 365-376. https://doi.org/10.1111/micc.12028
Leblanc, Amanda J. ; Chen, Bei ; Dougherty, Patrick J. ; Reyes, Rafael A. ; Shipley, Robert D. ; Korzick, Donna H. ; Muller-Delp, Judy M. / Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles. In: Microcirculation. 2013 ; Vol. 20, No. 5. pp. 365-376.
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abstract = "Objective: The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age-induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex-specific. Methods: Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor-specific signaling. Results: In intact arterioles from males, ET-induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age-related differences in responses to ET; however, denudation of arterioles from both sexes revealed age-related differences in ETa-mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age-related changes in ET signaling occur downstream of ET receptors. Conclusions: Thus, aging-induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex-specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.",
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Leblanc, AJ, Chen, B, Dougherty, PJ, Reyes, RA, Shipley, RD, Korzick, DH & Muller-Delp, JM 2013, 'Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles', Microcirculation, vol. 20, no. 5, pp. 365-376. https://doi.org/10.1111/micc.12028

Divergent effects of aging and sex on vasoconstriction to endothelin in coronary arterioles. / Leblanc, Amanda J.; Chen, Bei; Dougherty, Patrick J.; Reyes, Rafael A.; Shipley, Robert D.; Korzick, Donna H.; Muller-Delp, Judy M.

In: Microcirculation, Vol. 20, No. 5, 01.07.2013, p. 365-376.

Research output: Contribution to journalArticle

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AU - Leblanc, Amanda J.

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AU - Dougherty, Patrick J.

AU - Reyes, Rafael A.

AU - Shipley, Robert D.

AU - Korzick, Donna H.

AU - Muller-Delp, Judy M.

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N2 - Objective: The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age-induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex-specific. Methods: Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor-specific signaling. Results: In intact arterioles from males, ET-induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age-related differences in responses to ET; however, denudation of arterioles from both sexes revealed age-related differences in ETa-mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age-related changes in ET signaling occur downstream of ET receptors. Conclusions: Thus, aging-induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex-specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.

AB - Objective: The risk for cardiovascular disease increases with advancing age; however, the chronological development of heart disease differs in males and females. The purpose of this study was to determine whether age-induced alterations in responses of coronary arterioles to the endogenous vasoconstrictor, endothelin, are sex-specific. Methods: Coronary arterioles were isolated from young and old male and female rats to assess vasoconstrictor responses to endothelin (ET), and ETa and ETb receptor inhibitors were used to assess receptor-specific signaling. Results: In intact arterioles from males, ET-induced vasoconstriction was reduced with age, whereas age increased vasoconstrictor responses to ET in intact arterioles from female rats. In intact arterioles from both sexes, blockade of either ETa or ETb eliminated age-related differences in responses to ET; however, denudation of arterioles from both sexes revealed age-related differences in ETa-mediated vasoconstriction. In arterioles from male rats, ETa receptor protein decreased, whereas ETb receptor protein increased with age. In coronary arterioles from females, neither ETa nor ETb receptor protein changed with age, suggesting age-related changes in ET signaling occur downstream of ET receptors. Conclusions: Thus, aging-induced alterations in responsiveness of the coronary resistance vasculature to endothelin are sex-specific, possibly contributing to sexual dimorphism in the risk of cardiovascular disease with advancing age.

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