Cardiovascular effects of carnosine

Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide found in var ious cells at millimolar concentration with its specific function(s) largel y unknown. Our interests in therapeutic peptides led to the discovery that carnosine dramatically increases contractility when perfused into isolated rat hearts. Carnosine's effects are not mediated by histaminic or beta-adre nergic receptors or by increasing cyclic AMP, but carnosine does cause a ri se in myoplasmic Ca2+ concentration. In chemically skinned cardiac cells, c arnosine releases calcium, produces contracture, and alters the contractile protein's tension response to calcium, Carnosine also acts directly on the ryanodine receptor calcium release channel producing large increases in op en state probability and dwelltime. In this manuscript, we will review stud ies which provide a basis for considering carnosine a modulator of calcium- regulated proteins in cardiac muscle cells and consequently an important de terminant of contractility and cardiac function.