Adrenoceptors and Adaptive Mechanisms in the Heart during Stress

Several cardiovascular disorders have been related to alterations in beta‐adrenoceptor (β‐AR) signaling at or beyond the receptor level. During the stress reaction, the sympathetic‐adrenal medullary system and the hypothalamus‐pituitary‐adrenal cortex axis are activated, causing β‐AR overstimulation and remodeling of the β 1 /β 2 /β 3 ‐AR ratio in cardiomyocytes. In a model of foot‐shock stress, we described decreased β 1 ‐AR signaling occurring simultaneously with increased β 2 ‐AR signaling, whereas the response to the nonconventional agonist, CGP12177, was not altered. These alterations may play an adaptive role to the increased sympathetic drive to the heart, protecting the cardiac tissue from the cardiotoxic effects mediated by β 1 ‐ARs overstimulation without altering cardiac output, since this would be sustained by the β 2 ‐AR, which would also protect myocytes from apoptosis. Moreover, the selective enhancement of the β 2 ‐AR population might help to diminish the risk of overstimulation since this adrenoceptor subtype couples to both, stimulatory G (Gs) and inhibitory G (Gi) proteins. On the other hand, in the model of neurogenic hypertension, the decrease in β 1 ‐AR–mediated response is not followed by increase in the β 2 ‐AR–mediated response. However, the response to CGP12177, which was desensitized 48 h after the surgery, was normalized 7 days after that, when β 1 ‐AR were downregulated. Therefore, both experimental models provided evidence that the classical isoform of β 1 ‐AR and the recently described low‐affinity isoform of β 1 ‐AR show independent behavior and provide the heart with adaptive mechanisms to increased sympathetic stimulation during stress.