Cardiac α1-Adrenoceptors and Inotropy

Cardiac α1-adrenoceptor stimulation elicits a positive inotropic effect because of myofilament Ca2+ sensitization with a small increase in Ca2+ transients predominantly mediated by α1B-adrenoceptors via the intracellular alkalinization and potential myosin light chain 2 phosphorylation. However, the α1-adrenoceptor– mediated 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 α1-adrenoceptor– mediated regulation is vulnerable being markedly influenced by experimental and pathophysiological conditions. Cardiac α1-adrenoceptors may have clinical relevance in that sympathomimetic amines including norepinephrine possess higher affinity to α1-adrenoceptors than β-adrenoceptors, and α1-adrenoceptors play a compensatory role in patients with heart failure. Modulation of cardiac α1-adrenoceptor–mediated signaling pathway could provide potential targets for the development of novel therapeutic strategy.