ROLES OF α 1A ‐ AND α 1B ‐ADRENOCEPTORS IN HEART: INSIGHTS FROM STUDIES OF GENETICALLY MODIFIED MICE

SUMMARY1 Several mouse strains have been prepared in which different subtypes of the α 1 ‐adrenoceptor (AR) are overexpressed or deleted. The phenotypes of the animals generated vary depending on whether the receptors are expressed specifically in heart or generally throughout the animal, but some overall conclusions can be drawn. 2 Heightened activity of α 1B ‐AR by overexpressing the receptors leads to depressed contractile responses to β‐AR activation, which may be related to activation of the inhibitory G‐protein G i . In contrast, α 1A ‐AR cause substantially heightened contractility when overexpressed in heart. 3 Overexpressed α 1B ‐AR predispose hearts to hypertrophy and worsen heart failure caused by pressure overload, whereas increased α 1A ‐AR expression does not influence hypertrophic responses and, furthermore, improves outcomes after pressure overload or myocardial infarction. 4 α 1A ‐Adrenoceptors mediate a preconditioning action to improve functional recovery after acute ischaemic insult, whereas α 1B ‐AR are ineffective. Both subtypes appear to protect from inositol 1,4,5‐trisphosphate generation and arrhythmogenesis in early postischaemic reperfusion. 5 Although some of the protective effects of heightened α 1A ‐AR drive may be related to the enhanced contractility, it is also possible that α 1A ‐AR protect from cardiomyocyte apoptotic responses.