The overall goals of the Laboratory of Cardiovascular Science are (1) to identify age-associated changes that occur within the cardiovascular system and to determine the mechanisms for these changes; (2) to study myocardial structure and function and to determine how age interacts with chronic disease states to alter function; (3) to study basic mechanisms in excitation-contraction coupling and how these are modulated by surface receptor signaling pathways in cardiac muscle; (4) to determine the chemical nature and sequence of intermediate reactions controlling the movement of ions through ionic channels and pumps present in myocardium, and how these are affected by aging and disease; (5) to determine mechanisms that govern neuro-hormonal behavioral aspects of hypertension; (6) to determine mechanisms of normal and abnormal function of vascular smooth muscle and endothelial cells; and (7) to establish the potentials and limitations of new therapeutic approaches such as gene transfer techniques. In meeting these objectives, studies are performed in human volunteers, intact animals, isolated heart and vascular tissues, isolated cardiac and vascular cells, and subcellular organelles.