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Early life stress in male mice induces superoxide production and endothelial dysfunction in adulthood.
Ho, Dao H; Burch, Mariah L; Musall, Benjamin; Musall, Jacqueline B; Hyndman, Kelly A; Pollock, Jennifer S.
Afiliação
  • Ho DH; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
  • Burch ML; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Department of Medicine, Augusta University, Augusta, Georgia.
  • Musall B; Department of Medicine, Augusta University, Augusta, Georgia.
  • Musall JB; Department of Medicine, Augusta University, Augusta, Georgia.
  • Hyndman KA; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
  • Pollock JS; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and Department of Medicine, Augusta University, Augusta, Georgia pollockj@uab.edu.
Am J Physiol Heart Circ Physiol ; 310(9): H1267-74, 2016 05 01.
Article em En | MEDLINE | ID: mdl-26921433
Early life stress (ELS) is a risk for cardiovascular disease in adulthood although very little mechanistic insight is available. Because oxidative stress and endothelial dysfunction are major contributors to cardiovascular risk, we hypothesized that ELS induces endothelial dysfunction in adult male mice via increased superoxide production. Studies employed a mouse model of ELS, maternal separation with early weaning (MSEW), in which litters were separated from the dam for 4 h/day [postnatal days (PD) 2-5] and 8 h/day (PD6-16), and weaned at PD17. Control litters remained undisturbed until weaning at PD21. When compared with control mice, thoracic aortic rings from adult male MSEW mice displayed significant endothelial dysfunction that was reversed by the superoxide scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD). PEG-SOD-inhibitable superoxide production by aortae from MSEW mice was significantly greater than observed in control aortae, although unaffected by nitric oxide synthase inhibition, suggesting that uncoupled nitric oxide synthase was not responsible for the accelerated superoxide production. Aortic SOD expression, plasma SOD activity, and total antioxidant activity were similar in MSEW and control mice, indicating unaltered antioxidant capacity in MSEW mice. Increased expression of the NADPH oxidase subunits, NOX2 and NOX4, was evident in the aortae of MSEW mice. Moreover, endothelial dysfunction and superoxide production in MSEW mice was reversed with the NADPH oxidase inhibitor, apocynin, indicating increased NADPH oxidase-dependent superoxide production and endothelial dysfunction. The finding that MSEW induces superoxide production and endothelial dysfunction in adult mice may provide a mechanistic link between ELS and adult cardiovascular disease risk.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Aorta Torácica / Estresse Psicológico / Vasodilatação / Endotélio Vascular / Superóxidos / Estresse Oxidativo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Aorta Torácica / Estresse Psicológico / Vasodilatação / Endotélio Vascular / Superóxidos / Estresse Oxidativo Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2016 Tipo de documento: Article