Abstract
Oxidative-nitrosative stress may play a role in age-associated cardiovascular disease as implied by recent studies.However, limited research has been conducted using aged female rodent models. In this study, we examined hearts obtained from 6-, 26-, and 30-month old female Fischer 344/Nnia x Brown Norway/BiNia (F344xBN) rats in order to examine how aging affects levels of cardiac oxidative-nitrosative stress and apoptosis. Oxidative (superoxide anion and 4-HNE) and nitrosative (protein nitrosylation) stress markers were increased 180 ± 17 %, 110 ± 3 %, and 14 ± 2 %, respectively in 30-month hearts compared to the hearts of 6-month female rats. Coincident with these changes in oxidative-nitrosative stress, aging was also found to be associated with increases in the number of Tdt-mediated dUTP nick labeling (TUNEL)-positive cardiomyocytes, alterations in the Bax/Bcl-2 ratio, and elevated cleavage of caspase-3. Regression analysis demonstrates significant correlation in the age-associated changes markers of oxidative–nitrosative stress with changes in apoptotic signaling. The findings from this descriptive study imply that age-associated increases in mitochondrial-mediated apoptosis may be associated with the increase in oxidative-nitrosative stress in the aging F344xBN female heart.
Highlights
Aging is thought to be a major risk factor for cardiovascular disease (CVD),and is associated with a loss of cardiomyocytes by apoptosis, and increases in tissue fibrosis which can lead to systolic and diastolic dysfunction [1,2,3,4,5]
Previous data has demonstrated increased levels of apoptosis and oxidative stress are associated with aging in the male heart, to our knowledge this is the first investigation to examine if these phenomena occur in the naturally menopausal aging female rat model [13,16]
Why aging may increase reactive oxygen species (ROS) levels is not yet fully understood recent data has suggested that alterations in enzymatic activity of the xanthine and NADPH oxidoreductases, the mitochondrial electron transport chain, nitric oxide synthase activity, and lipoxygenase/cyclooxygenase may function as potential contributors [22, 23]
Summary
Aging is thought to be a major risk factor for cardiovascular disease (CVD),and is associated with a loss of cardiomyocytes by apoptosis, and increases in tissue fibrosis which can lead to systolic and diastolic dysfunction [1,2,3,4,5]. Other studies have demonstrated that the mitochondria-mediated pathway of apoptosis was activated in the heart in ovariectomized rats and this appeared to occur coincident with decreased antioxidant enzyme activity and increased indices of oxidative stress [11, 12]. These data are suggestive of estrogen playing a protective role in the cardiovascular system, how the natural loss of estrogen with aging affects cardiac ROS levels is not well known
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