Exercise Training Reduces Age‐Dependent Elevation of Angiotensin II Type 1 receptor and NAD(P)H Oxidase

Abstract

Fibrosis in the aging heart impedes diastolic filling and increases arrhythmias. Previously, we demonstrated that exercise training (ET) reduced collagen I fibrosis and oxidative stress in the aging heart. Recent studies show that NAD(P)H oxidases (Nox) could be an important source of oxidative stress during the aging process, activated by renin‐angiotensin II‐aldosterone system (RAAS). Given that Nox and RAAS may elicit collagen accumulation in the aging heart, we tested the hypothesis that ET would alleviate age‐related upregulation of Nox (p47phox) and RASS (angotensin II receptor 1: ATR1) markers. Young (3 mo) and old (31 mo) FBNF1 rats were assigned into sedentary (YS, OS) and exercise (YE, OE) groups, with ET rats training on a treadmill 45 min/d, 5 d/wk for 12 wk. ET diminished web‐like geometry of connective tissue and large cardiomyocytes in the old age group. Aging increased p47phox–positive staining and protein expression 78.4% (p<.032) in the LV, while OE displayed lower p47phox‐positive staining, with protein abundance trending lower (−46.6%). gp91phox levels in OS trended higher 22.8% than YS. ATR1 was significantly elevated with age (+36.6%, p<.02), but was not significantly blunted with ET. Results indicate that exercise training may provide significant protection against Nox upregulation and thus fibrosis, while upstream regulation by ATR1 remains uncertain.