Cardiovascular effects of carnosine.

Carnosine (beta-alanyl-L-histidine) is an endogenous dipeptide found in various cells at millimolar concentration with its specific function(s) largely 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-adrenergic receptors or by increasing cyclic AMP, but carnosine does cause a rise in myoplasmic Ca(2+) concentration. In chemically skinned cardiac cells, carnosine 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 open state probability and dwelltime. In this manuscript, we will review studies which provide a basis for considering carnosine a modulator of calcium-regulated proteins in cardiac muscle cells and consequently an important determinant of contractility and cardiac function.