High levels of epinephrine may trigger apical cardiodepression in Takotsubo cardiomyopathy via β2AR-Gi signaling as a cardioprotective mechanism against catecholamine toxicity.
We suggest that biased agonism of epinephrine for β(2)AR-G(s) at low concentrations and for G(i) at high concentrations underpins the acute apical cardiodepression observed in Takotsubo cardiomyopathy, with an apical-basal gradient in β(2)ARs explaining the differential regional responses. We suggest this epinephrine-specific β(2)AR-G(i) signaling may have evolved as a cardioprotective strategy to limit catecholamine-induced myocardial toxicity during acute stress.
Paur et al. (2012) studied this question.