Adaptation to continuous and intermittent normobaric hypoxia is associated with similar alterations in the myocardial β-adrenergic signaling system
Abstrakt
Adaptation to chronic hypoxia can protect the heart against acute ischemic injury under certain conditions. However, the molecular mechanisms engaged in adaptive changes of the heart are still not well understood.
Here we assessed the effects of adaptation to 3-week continuous (CNH) or intermittent normobaric hypoxia (INH; 23 h hypoxia followed by 1 h reoxygenation) on β-adrenergic signaling in the rat myocardium. Exposure to both regimens of hypoxia resulted in loss of body weight and marked right ventricular (RV) hypertrophy.
Whereas there was no significant change in β-adrenoceptors (β-ARs) in the left ventricles (LV), the total number of these receptors was reduced by about 25% in RV preparations from animals adapted to hypoxia. Discrimination of β-AR receptor subtypes indicated that the diminution of these receptors was largerly attributable to the loss of β1-ARs.
Chronic hypoxia did not substantially influence the expression of the dominant isoforms of myocardial adenylyl cyclase (AC 5/6) and the stimulatory G proteins. On the other hand, enzyme activity of AC stimulated through the G proteins was decreased in the RV and increased in the LV after exposure to hypoxia.
These data suggest that chronic normobaric hypoxia may strongly affect the β-adrenergic signaling system. Although CNH and INH may display different cardioprotective potential, the former being protective and the latter nonprotective, adaption to both these regimens was not accompanied by profoundly different changes on the level of myocardial β-adrenergic signaling.