Heart International / Vol. 2 no. 2, 2006 / pp. 78-81 © Wichtig Editore, 2006 Discovering a new role for the atrial natriuretic peptide: A novel risk factor for cardiovascular diseases SPERANZA RUBATTU, MASSIMO VOLPE Division of Cardiology, II Faculty of Medicine, University of Rome “La Sapienza”, Sant’Andrea Hospital, Rome - Italy; IRCCS Neuromed, Pozzilli (Is) - Italy ABSTRACT: Atrial natriuretic peptide, a diuretic, natriuretic and vasorelaxant hormone, is also involved in the regulation of cardiovascular remodeling and it has been recently shown to be sig- nificantly associated with higher occurrence of cardiovascular diseases. In fact, high plasma ANP levels predict higher mortality rate for cardiovascular events. Moreover, ANP gene alter- ations are associated with higher risk of cardiovascular intermediate phenotypes, such as left ventricular hypertrophy, and of cardiovascular diseases, such as stroke and hypertension. Thus, the characterization of ANP plasma levels, and of ANP genotype for known mutations can be proposed as an informative component of the individual cardiovascular risk profile. (Heart In- ternational 2006; 2: 78-81) KEY WORDS: Atrial natriuretic peptide, Cardiovascular risk, Genetic INTRODUCTION The atrial natriuretic peptide (ANP) is a well known component of the natriuretic peptide family, which also includes BNP and CNP, and plays an important role in the regulation of electrolytes and water balance through its diuretic and natriuretic effects, as well as of vasomo- tor tone through its vasorelaxant effect. Thus, ANP maintains blood pressure homeostasis. Moreover, through the reduction of preload and afterload as a con- sequence of its hemodynamic effects, ANP is a key reg- ulator of cardiac performance (1). Since its discovery in 1981 (2), the atrial natriuretic peptide has been largely investigated in the pathophys- iology of several cardiovascular diseases, such as hy- pertension, heart failure, coronary and cerebrovascular disease (3). Thus, circulating and cardiac levels of ANP are di- rectly correlated with the degree of cardiac dysfunction 1826-1868/078-4$15.00/0 in heart failure (4). Elevated ANP levels are also a hall- mark of arterial hypertension (5, 6). However, only through the recent introduction of molecular genetic techniques have we had the chance to learn important new information on the direct contri- bution of ANP to the individual susceptibility to develop cardiovascular diseases (Fig. 1). ANP and the risk of cerebro-vascular disease Evidence from an animal model of stroke, the stroke- prone spontaneously hypertensive rat, implicated, for the first time, the gene encoding ANP as a direct con- tributor to stroke susceptibility. In fact, the ANP gene was found to map at the peak of linkage of a “protec- tive” quantitative trait locus for stroke proneness identi- fied in the SHRsp animal model (7). A subsequent de- tailed analysis of the rat ANP gene revealed structural