Cardiac α 1 -Adrenoceptors and Inotropy

C ardiac α 1 -adrenoceptor stimulation elicits a posi- tive inotropic effect because of myofilament Ca 2+ sensitization with a small increase in Ca 2+ transients predominantly mediated by α 1B -adrenoceptors via the intracellular alkalinization and potential myosin light chain 2 phosphorylation.However, the α 1 -adrenoceptormediated inotropy exhibits a wide range of species-dependent variation.In addition, it displays remarkable regional and subtype-dependent variations among species.The signaling pathway for α 1 -adrenoceptormediated regulation is vulnerable being markedly influenced by experimental and pathophysiological conditions.Cardiac α 1 -adrenoceptors may have clinical relevance in that sympathomimetic amines including norepinephrine possess higher affinity to α 1 -adrenoceptors than β-adrenoceptors, and α 1 -adrenoceptors play a compensatory role in patients with heart failure.Modulation of cardiac α 1 -adrenoceptor-mediated signaling pathway could provide potential targets for the development of novel therapeutic strategy.The role of cardiac α 1 -adrenoceptors in regulation of myocardial contractility, including mechanism of action, signaling pathway, and pathophysiological and clinical significance, has been less clarified compared with the well-established β-adrenoceptor-mediated regulation.In this viewpoint, I will focus on the state-of-the-art of cardiac α 1 -adrenoceptormediated basic mechanism and its pathophysiological relevance in relation to clinical implications. Cardiac α 1 -Adrenoceptors and Inotropy