1. With the generation of gene knockout (KO) or transgenic overexpression (TG) mouse models targeting
adrenoceptors (AR), recent studies in vivo have investigated the role of AR subtypes in pressure overload-induced left ventricular (LV)
hypertrophy and remodelling. 2. Although subjecting alpha(1B)-KO mice to transverse aortic constriction (TAC) did not reveal significant phenotype differences compared with controls, mice deficient in both alpha(1A)- and alpha(1B)-AR responded to TAC with poor survival, increased cardiomyocyte apoptosis, more severe
fibrosis and dysfunction, but a similar degree of LV
hypertrophy, compared with wild-type littermates. Following TAC, alpha(1B)-TG mice developed more severe
hypertrophy, interstitial
fibrosis and
LV dysfunction. In contrast, overexpression of alpha(1A)-AR preserved cardiac function and reduced death from
heart failure without affecting the degree of LV
hypertrophy. Thus, alpha(1A)- and alpha(1B)-adrenoceptor signalling impacts differently on myocardial adaptation to pressure overload. 3. The absence of both beta(1)- and beta(2)-AR significantly suppressed pressure overload-evoked
hypertrophy,
fibrosis and expression of inflammatory or fibrogenic genes. Conversely, studies on beta(2)-TG mice with TAC revealed adverse consequences, including accelerated development of
heart failure, poor survival and more severe interstitial
fibrosis, but a comparable degree of
hypertrophy compared with wild-type littermates. 4. Collectively, these findings suggest that the effect of ARs on pressure overload-induced myocardial adaptation is subtype specific. Whereas activation of alpha(1B)-AR or beta(2)-AR contributes to maladaptation and the onset of
heart failure, activation of alpha(1A)-AR or inactivation of beta(2)-AR is beneficial in the setting of chronic pressure overload.