ROLES OF α1A‐ AND α1B‐ADRENOCEPTORS IN HEART: INSIGHTS FROM STUDIES OF GENETICALLY MODIFIED MICE

Author:
Publisher website
Google Scholar
Abstract
SUMMARY: Several mouse strains have been prepared in which different subtypes of the α1‐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. Heightened activity of α1B‐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 Gi. In contrast, α1A‐AR cause substantially heightened contractility when overexpressed in heart. Overexpressed α1B‐AR predispose hearts to hypertrophy and worsen heart failure caused by pressure overload, whereas increased α1A‐AR expression does not influence hypertrophic responses and, furthermore, improves outcomes after pressure overload or myocardial infarction. α1A‐Adrenoceptors mediate a preconditioning action to improve functional recovery after acute ischaemic insult, whereas α1B‐AR are ineffective. Both subtypes appear to protect from inositol 1,4,5‐trisphosphate generation and arrhythmogenesis in early postischaemic reperfusion. Although some of the protective effects of heightened α1A‐AR drive may be related to the enhanced contractility, it is also possible that α1A‐AR protect from cardiomyocyte apoptotic responses.

This publication has 34 references indexed in Scilit: