Sex differences in angiotensin II responses contribute to a differential regulation of cox-mediated vascular dysfunction during aging.
Exp Gerontol
; 85: 71-80, 2016 12 01.
Article
em En
| MEDLINE
| ID: mdl-27713002
ABSTRACT
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 12months of age (M). Contribution of RAS was determined by treating mice from 3M to 12M with the AngII type 1 receptor blocker losartan (0.6g/L in the drinking water). At 12M, 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 12M males. Aging also diminished ACh relaxation in males, but did not modify female responses. Treatment of aortas with indomethacin (10µM) restored the impaired endothelium-dependent relaxation in 12M 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 12M 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Renina-Angiotensina
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Envelhecimento
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Angiotensina II
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Prostaglandinas
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Fatores Sexuais
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Bloqueadores do Receptor Tipo 1 de Angiotensina II
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Exp Gerontol
Ano de publicação:
2016
Tipo de documento:
Article