Heart Failure

Abstract

See related article, pp 327–332 Atrial and brain natriuretic peptides (ANP and BNP) possess important regulatory cardiorenal functions, such as promoting natriuresis, diuresis, vasodilatation, and activation of antihypertrophic responses on pathophysiological stress. Release of ANP and BNP is significantly increased in response to atrial and ventricular stretch, respectively. Both ANP and BNP are produced and stored as prohormones and are present in the circulation as a mixture of propeptide and active 28- and 32-amino acid, carboxyl-terminal peptide hormones, respectively.1 Both ANP and BNP bind to the natriuretic peptide receptor-A, which is coupled to particulate guanylate cyclase to generate cGMP, the primary second messenger mediating downstream signaling cascades in target tissues. Despite stimulation of the same receptor, the physiological effects of ANP and BNP are somewhat different: ANP predominantly regulates sodium-water homeostasis and blood pressure, whereas BNP has more antihypertrophic effects, although there is substantial overlap.1 In theory, increases in generation of ANP and BNP in response to myocardial stretch should occur as part of compensatory mechanism(s) to restore homeostatic balance. However, the lusitropic, antihypertrophic, and natriuretic effects of ANP and BNP are significantly attenuated in congestive heart failure despite a considerable apparent increase in plasma concentrations. It is now increasingly accepted that the key reason for this discrepancy is because of variable activation/processing of natriuretic peptides, resulting in much greater proportion …