Age Effects on the Adaptive Response of the Female Rat Heart Following Aortic Constriction

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Abstract
Aging is associated with adaptations in the hearts of mammals that diminish the reserve capacity to meet hemodynamic loading challenges. To evaluate potential mechanisms of this phenomenon, the following hypotheses were tested: compared with hearts of adult rats, hearts of aged rats undergoing aortic constriction will exhibit (a) a lower concentration of myofibrillar proteins, (b) a reduced sensitivity to extracellular calcium, and (c) a reduced coronary perfusion. Female Fischer 344 rats aged 9 months (adult) and 27 months (aged) were assigned to control (C) or aortic-constriction (AC) groups and studied at 7 and 28 days post-AC, yielding six groups of rats. Analysis of variance was used to examine the effects of age and AC. The left ventricular (LV) mass/body mass ratio expressed a percentage of age-matched control value averaged AC-7adult, 111%; AC-28adult, 120%; AC-7aged, 106%; AC-28aged, 123% (AC, p < .01). As a percentage of adult rats values, the pressure-generating capacity of the LV averaged Caged, 99%; AC-7aged, 92%; AC-28aged, 92% (age, p < .05). There were no differences attributable to age or AC in either myofibrillar protein concentration or calcium sensitivity. There was, however, a significantly lower concentration of nonmyofibrillar protein (∼10%) in the hearts of all three groups of aged rats compared with the adult rats that was unaltered by AC. The percentages of LV myosin heavy chain in the α-isoform were Cadult, 77%; AC-7adult, 66%; AC-28adult, 66%; Caged, 45%; AC-7aged, 41%; AC-28aged, 32% (age, p < .01; AC, p < .01). Coronary flow per gram of tissue averaged 9% lower in all three of the aged groups compared with the adult rats and was not significantly affected by AC (age, p < .05). The data suggest that a reduction in nonmyofibrillar protein and a reduced coronary flow, rather than changes in calcium sensitivity or myofibrillar protein, are associated with an impairment in the adaptive response of the aged heart.