Sex differences in angiotensin II responses contribute to a differential regulation of cox-mediated vascular dysfunction during aging

Gustavo Costa, Manel Garabito, Francesc Jiménez-Altayó, Yara Onetti, Manel Sabate, Elisabet Vila, Ana Paula Dantas

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

© 2016 Elsevier Inc. Aging is a cardiovascular risk factor partially related to activation of the Renin-Angiotensin System (RAS). RAS activation is also influenced by sex. In this regard, our study aims to determine whether sex-associated differences in RAS contribute to a differential regulation of vascular aging and associated dysfunction. Male and female outbreed CD-1 mice were studied at 3 and 12 months of age (M). Contribution of RAS was determined by treating mice from 3 M to 12 M with the AngII type 1 receptor blocker losartan (0.6 g/L in the drinking water). At 12 M, contractions to AngII were higher in males compared to females (P < 0.05). This effect was paralleled by a decrease in AngII type 2 receptors in 12 M males. Aging also diminished ACh relaxation in males, but did not modify female responses. Treatment of aortas with indomethacin (10 μM) restored the impaired endothelium-dependent relaxation in 12 M males, suggesting an increase of cyclooxygenase (COX)-derived vasoconstrictors in aged males. Chronic treatment of mice with losartan also improved endothelium-dependent relaxation. Besides, losartan significantly decreased COX-2 expression and activity in 12 M male, with a minor effect in aged females. Aging increases AngII contraction and induces endothelial dysfunction differently in males and females. In aged males, RAS contributed to increased COX-2 expression and activity, which in turn may lead to vascular dysfunction.
Original languageEnglish
Pages (from-to)71-80
JournalExperimental Gerontology
Volume85
DOIs
Publication statusPublished - 1 Dec 2016

Keywords

  • Endothelial dysfunction
  • Prostaglandin
  • Renin-angiotensin system
  • Sex-differences
  • Vascular aging

Fingerprint Dive into the research topics of 'Sex differences in angiotensin II responses contribute to a differential regulation of cox-mediated vascular dysfunction during aging'. Together they form a unique fingerprint.

  • Cite this