© 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.
- Endothelial dysfunction
- Renin-angiotensin system
- Vascular aging
Costa, G., Garabito, M., Jiménez-Altayó, F., Onetti, Y., Sabate, M., Vila, E., & Dantas, A. P. (2016). Sex differences in angiotensin II responses contribute to a differential regulation of cox-mediated vascular dysfunction during aging. Experimental Gerontology, 85, 71-80. https://doi.org/10.1016/j.exger.2016.09.020