New insights into the cardiac natriuretic peptides.

Abstract

Cardiac natriuretic peptides contribute importantly to the maintenance of sodium and volume homeostasis in health and disease. The hemodynamic, renal, and endocrinologic effects of these peptides have been the subject of intense basic and clinical investigation for more than 15 years. In particular, the activation of the cardiac natriuretic peptide system in patients with LV dysfunction has generated considerable interest recently, because elevated circulating levels of these substances have important prognostic and therapeutic implications. Unlike the vasoconstrictor neurohormones that are also activated in the setting of LV dysfunction, such as norepinephrine, the renin-angiotensin system, and arginine vasopressin, which play a pathogenetic role in the progression of ventricular dysfunction and development of heart failure, the cardiac natriuretic peptides have beneficial, compensatory actions to promote systemic arterial dilation, natriuresis, diuresis, and renin inhibition. ANP is a 28–amino acid peptide synthesized and secreted by the atria.1 2 3 ANP is stored in the myocyte as a 126–amino acid prohormone. On secretion, the prohormone is split into an N-terminal moiety of 98 amino acids (N-ANP) and the biologically active ANP in equimolar amounts.3 N-ANP is more easily measured; it has a significantly longer half-life in plasma compared with ANP, which is very short lived (half-life, 2.5 minutes2 ) and thus has up to 50 times the plasma concentration of ANP.2 3 4 In addition, N-ANP is more stable under laboratory conditions for measurement.5 It is now well established that circulating ANP levels are increased in patients with chronic congestive heart failure in proportion to the severity of the disease4 6 7 8 and are elevated in patients with asymptomatic LV dysfunction.9 10 Although there is a relation between plasma ANP levels and atrial pressure, it is generally believed that atrial wall stress and stretch, rather than atrial …