The objectives of the proposed research, in the broadest term, are to establish the mechanism of action of cyclic GMP, and to explore and define the roles of cyclic GMP-dependent protein kinase in physiology and pathology of the heart. Attempts will be made to find the sites of action of the cyclic GMP-dependent enzyme and to correlate phosphorylation of the "substrate" proteins with possible changes in their properties. Attempts will also be made to establish patterns of changes in the content and level of cyclic GMP and the cyclic GMP-dependent enzyme, compared to those cyclic AMP and cyclic AMP-dependent protein kinase, in the heart under certain physiologic (such as development and exercise-trained) and pathologic (such as hypertrophy, hyperplasia, and myopathy) conditions, so that the regulatory roles of the cyclic GMP-mediated processes can be suggested.