The Roles of Cardiovascular H₂-Histamine Receptors Under Normal and Pathophysiological Conditions

This review addresses pharmacological, structural and functional relationships among H₂-histamine receptors and H₁-histamine receptors in the mammalian heart. The role of both receptors in the regulation of force and rhythm, including their electrophysiological effects on the mammalian heart, will then be discussed in context. The potential clinical role of cardiac H₂-histamine-receptors in cardiac diseases will be examined. The use of H₂-histamine receptor agonists to acutely increase the force of contraction will be discussed. Special attention will be paid to the potential role of cardiac H₂-histamine receptors in the genesis of cardiac arrhythmias. Moreover, novel findings on the putative role of H₂-histamine receptor antagonists in treating chronic heart failure in animal models and patients will be reviewed. Some limitations in our biochemical understanding of the cardiac role of H₂-histamine receptors will be discussed. Recommendations for further basic and translational research on cardiac H₂-histamine receptors will be offered. We will speculate whether new knowledge might lead to novel roles of H₂-histamine receptors in cardiac disease and whether cardiomyocyte specific H₂-histamine receptor agonists and antagonists should be developed.