Adrenoceptors and adaptive mechanisms in the heart during stress.

Several cardiovascular disorders have been related to alterations in beta-adrenoceptor (beta-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 beta-AR overstimulation and remodeling of the beta(1)/beta(2)/beta(3)-AR ratio in cardiomyocytes. In a model of foot-shock stress, we described decreased beta(1)-AR signaling occurring simultaneously with increased beta(2)-AR signaling, whereas the response to the nonconventional agonist, CGP12177, was not altered.

Stress and cardiac beta adrenoceptors.

Most modern theories about stress recognize that although stress is not a disease, it may be the trigger for the majority of diseases when allostatic overload has been generated. During stress, the glucocorticoids and catecholamines play a key role in the regulation of physiological parameters and homeostasis during stress. In the heart, positive chronotropic, inotropic, and lusitropic responses to catecholamines are mediated by various subtypes of adrenergic receptors (beta-ARs), mainly beta1- and beta2-adrenergic receptors.

Evidence for two atypical conformations of beta-adrenoceptors and their interaction with Gi proteins.

In this study, we investigated whether the responses of right atria from sinoaortic denervated rats to CGP12177 (4(3-t-butylamino-2-hydroxypropoxy benzidimidazole-2 one, hydrochloride)), isoprenaline and norepinephrine desensitized in parallel and whether CGP12177 interacted with distinct conformations of beta-adrenoceptors. Right atria from rats 48 h after sinoaortic denervation were subsensitive to isoprenaline, norepinephrine and CGP12177. One week after sinoaortic denervation, the sensitivity to CGP12177 had recovered whereas the responses to isoprenaline and norepinephrine were still subsensitive, suggesting that the binding sites for these molecules showed independent behavior.

Glucocorticoid receptor and Beta-adrenoceptor expression in epididymal adipose tissue from stressed rats.

Adipocytes isolated from epididymal adipose tissue of foot-shock stressed rats are supersensitive to isoprenaline and subsensitive to norepinephrine. These alterations are probably mediated by a stress-induced increase in plasma corticosterone levels. We investigated whether foot-shock stress modifies the expression of glucocorticoid receptors (GRs) and beta-adrenergic protein receptors (beta-ARs) in epididymal adipose tissue from rats submitted to one daily foot-shock session on three consecutive days.