The overall objective of this Program Project Grant is to study the regulation of the circulation in pathological states. It represents a coordinated effort on the parts of several investigators in clinical and in basic science specialities to study in a systematic way cellular mechanisms of vascular properties, as well as cardiovascular control mechanisms in hypertension, myocardial ischemia, heart failure and various abnormal circulatory states. The approach to the work on cellular mechanisms, as well as cardiovascular control mechanisms has included studies on cultured vascular cells, isolated vessels, animal models of disease, normal human subjects and patients. Each investigator has applied his special expertise in the laboratory to the solution of specific problems and the interaction between all investigators has provided the appropriate environment for the emergence of new ideas and new directions for research. The current program has had a major emphasis on cardiovascular control mechanisms and is outlined as follows: 1. Cellular Mechanisms in Physiologic and Pathophysiologic States; Mechanisms of Increased Reactivity of Arterial Muscle in SHR; Adrenergic Regulation of Cellular Function in Vascular Smooth Muscle. 2. Cardiovascular Control Mechanisms; Neurohumoral Control in Physiologic States; Control Mechanisms in Hypertension, Myocardial Ischemia and Heart Failure. These include: Neurohumoral Control; Mechanical Stress Factors; Myocardial Ischemia; Renal Factors. Control Mechanisms in Other Abnormal Circulatory States. Bibliographic references: Eckberg, D. L., Cavanaugh, M. S., Mark, A. L. and Abboud, F. M. A Simplified Neck Suction Device for Activation of Carotid Baroreceptors. J. Lab Clin. Med. 85:167, 1975. Eckberg, D. L. and Abboud, F. M. Mechanisms Mediating Bradycardia Resulting from Baroreceptor Activation in Man. Circ. Res. (In Revision), 1975.