EFFECTS OF CALORIC RESTRICTION ON CARDIAC, MITOCHONDRIAL FUNCTION AND THE REDOX STATE DURING ISOPROTERENOL-INDUCED CARDIAC HYPERTROPHY IN VIVO.
mitochondria. caloric restriction. cardiac hypertrophy. oxidative stress. free radicals. adrenergic signaling.
Cardiac hypertrophy is characterized by an increase in heart size due to intracellular
stimuli acquired from pressure or volume overload. Although it is an adaptive and
transient response, it often evolves into congestive heart failure, causing heart failure.
Mitochondrial dysfunctions are involved in the development of cardiac pathologies and
are generally associated with defects in the electron transport chain, Ca2+ overload,
reactivation of cardiac genes and, mainly, increased oxidative stress. On the other
hand, calorie restriction (CR) is a nutritional intervention that protects against cardiac
hypertrophy by decreasing oxidative stress and improving mitochondrial function. In
this study, it will be shown that this dietary intervention prevents the elevation of cardiac
proteins, avoids the reprogramming of the atrial natriuretic factor and blocks the
increase in the index of heart weight per length of the tibia (mg/cm), parameters
observed in hypertrophic hearts. These results suggest that CR inhibits pathological
cardiac growth while reducing mitochondrial reverse electron transport-induced
hydrogen peroxide formation and improving mitochondrial content. Additionally, RC
attenuated Ca2+-induced mPTP opening in mitochondria isolated from mice treated
with isoproterenol. In addition, CR blocked the negative correlation of antioxidant
enzymes (superoxide dismutase and glutathione peroxidase activity), leading to the
maintenance of sulfhydryl and glutathione protein levels. Given the nature of
isoproterenol-induced cardiac hypertrophy, we investigated whether CR could alter
cardiac β-adrenergic sensitivity. Thus, using isolated rat hearts in a Langendorff
system, it was seen that rats with CR (similar to controls) preserved β-adrenergic
signaling. In contrast, hypertrophic rat hearts (treated for seven days with
isoproterenol) were insensitive to β-adrenergic activation with isoproterenol (50 nM).
These results indicate that CR has beneficial effects against hypertrophic
cardiomyopathy and may contribute to the prevention and/or treatment of
complications related to cardiac hypertrophy and other cardiovascular diseases.