A Janus-Faced Role for Atrial Natriuretic Peptide in Myocardial Infarction?

The biological significance of atrial natriuretic peptide (ANP) has been studied exhaustively from a physiological, pathological, pharmacological, and diagnostic standpoint. This member of the natriuretic peptide family exerts a profile of complementary effects in the cardiovascular system, including natriuretic, diuretic, vasodilator, anti–renin–angiotensin–aldosterone system, antihypertrophic, and lipolytic activity to regulate blood volume, blood pressure, and maintain cardiac structure and function. Despite this extensive cytoprotective profile, pharmacological manipulation of ANP and natriuretic peptides in a more general sense has not been exploited therapeutically to the extent that might have been anticipated. Recombinant ANP (Carpertide) and brain natriuretic peptide (BNP; Nesiritide) are licensed for treatment of acute heart failure in some territories without overwhelming evidence from large-scale, randomized controlled trials. Only recently, LCZ696, a novel molecule combining the angiotensin receptor blocker valsartan with sacubitril, an inhibitor of neutral endopeptidase (an enzyme that hydrolyses and inactivates natriuretic peptides and many other vasoactive mediators), was shown to produce an approximate 20% reduction in cardiovascular death and hospitalization compared with enalapril in patients with heart failure and is now licensed for this disorder (LCZ696 produced an increase in urinary cGMP levels, inferring that it was increased natriuretic peptide biology that underpinned its therapeutic effect). Besides these limited examples, ANP and BNP have also been shown to reduce infarct size and improve left ventricular function after acute myocardial infarction (MI) in early phase trials. Could this represent a further indication in which harnessing natriuretic peptide bioactivity will be valuable therapeutically? In an intriguing and pertinent study published in this issue of Circulation Research, Chen et al present important new data that add to the understanding of the role(s) of ANP (and BNP) after MI and urge caution that although the net effect might be positive, it is not necessarily all one way traffic.