Food restriction alters the age-related decline in cardiac beta-adrenergic responsiveness

The responsiveness of the heart to beta-adrenergic receptor stimulation declines with age. The aim of this study was to determine whether food restriction (FR), the most effective means of retarding the aging processes, affects the loss of beta-adrenergic responsiveness. Male Fisher 344 rats, fed either ad libitum (Group A) or allowed to eat only 60% of what Group A rats consumed (Group B), were sacrificed at 4, 11 or 22-28 months of age. The hearts were isolated and perfused via the Langendorff method. Ventricular pressure-volume curves were constructed to determine the optimal volume for pressure development and concentration-response curves to isoproterenol were obtained at this optimal volume. Interestingly, the ventricular pressure-volume curve for 4 month Group B lay to the left of all the other groups, suggesting that hearts from younger FR rats possessed higher contractility than the other groups. In the unstimulated heart, aging was associated with a slower relaxation phase of contraction and FR further slowed the relaxation. The maximum response of the heart to isoproterenol declined with age and the decline was unaffected by FR. The concentration-response curves of hearts from older rats were generally shifted to the right of the younger animals, while FR shifted the curves to the left toward greater sensitivity to beta-adrenergic stimulation. The EC50s for isoproterenol increased with age, indicating a decrease in the responsiveness of the heart to beta-adrenergic receptor stimulation. In contrast, FR decreased the isoproterenol EC50, suggesting an enhanced responsiveness. These results demonstrate that FR can retard some aging changes (loss in beta-adrenergic responsiveness), while it enhances others (increase in relaxation times).