Human Cardiorenal Physiology and Therapeutics. This program based in the General Clinical Research Center has pursued in humans with heart failure the understanding of physiological mechanisms which contribute to regulation of renal function and its impairment in the heart failure syndrome. Two areas of major focus are the early asymptomatic phase of human heart failure and secondly its end-stage in which the cardiorenal syndrome is a critical clinical challenge with high morbidity. In early heart failure, this program is pursuing novel therapeutic strategies related to the natriuretic peptide system specifically the innovative use of chronic protein therapy with the natriuretic peptide BNP to maintain and preserve cardiorenal function and myocardial structure. Secondly, the strategy to combine PDE V inhibition with native natriuretic peptides or novel synthetic peptides to enhance impaired renal function in humans with cardiorenal system is built upon potentiating the cGMP/natriuretic peptide signaling pathway in the kidneys.