The Many Possible Benefits of Natriuretic Peptides After Myocardial Infarction

Abstract

Natriuretic peptides (NPs) are well-known markers of the ventricular hypertrophic response, as documented in many studies performed either in animals or with cultured cardiomyocytes. In recent years, evidence has been mounting that NPs are in fact negative regulators of the hypertrophic response, as reviewed recently.1 In this light, NPs appear as endogenous cardioprotective agents of which expression increases in reaction to myocardial pathological conditions, but it is still unclear to which extent these agents may actually decrease mortality. In this issue of Hypertension , Nakanashi et al2 show that when myocardial infarction (MI) is induced by permanent occlusion of the coronary artery, mortality by heart failure is increased in knockout mice with inactivation of the gene coding for the NP receptor guanylyl cyclase-A (GC-A). Beyond these short-term effects, inactivation of GC-A also worsens post-MI chronic ventricular remodeling. Although the present study does not show whether these chronic remodeling processes also increase mortality at a later stage, the remodeling is accompanied by ventricular enlargement and decreased fractional shortening, both of which usually associate with poor prognosis. The importance of these data is enhanced by the fact that increasing numbers of studies are investigating the utility of recombinant NPs in humans.3 However, several questions remain concerning the particular modes of action of NPs. One issue concerns the question of whether NPs work via peripheral mechanisms or via a direct action on the myocardium. Importantly, congestive heart failure is accompanied by volume expansion, and the present article shows that the natriuresis and diuresis are decreased in GC-A knockout animals during the 4 days that follow MI, thus possibly contributing to increased heart failure during …