Mechanisms of renal hyporesponsiveness to BNP in heart failure.

Abstract

The B-type natriuretic peptide (BNP), a member of the family of vasoactive peptides, is a potent natriuretic, diuretic, and vasodilatory peptide that contributes to blood pressure and volume homeostasis. These attributes make BNP an ideal drug that could aid in diuresing a fluid-overloaded patient who had poor or worsening renal function. Despite the potential benefits of BNP, accumulating evidence suggests that simply increasing the amount of circulating BNP does not necessarily increase natriuresis in patients with heart failure (HF). Moreover, despite high BNP levels, natriuresis falls when HF progresses from a compensated to a decompensated state, suggesting the emergence of renal resistance to BNP. Although likely multifactorial, several mechanisms have been proposed to explain renal hyporesponsiveness in HF, including, but not limited to, decreased renal BNP availability, down-regulation of natriuretic peptide receptors, and altered BNP intracellular signal transduction pathways. Thus, a better understanding of renal hyporesponsiveness in HF is required to devise strategies to develop novel agents and technologies that directly restore renal BNP efficiency. It is hoped that development of these new therapeutic approaches will serve to limit sodium retention in patients with HF, which may ultimately delay the progression to overt HF.