Although the precise reasons why patients with LV dysfunction may remain asymptomatic is not certain, one potential explanation is that a number of compensatory mechanisms become activated in the presence of cardiac injury and/or LV dysfunction allowing patients to sustain and modulate LV function for a period of months to years. The compensatory mechanisms that have been described thus far include (1) activation of the renin-angiotensin-aldosterone system (RAAS) and the adrenergic nervous system, which are responsible, respectively, for maintaining cardiac output through increased retention of salt and water (Fig. 252-2) and (2) increased myocardial contractility. In addi- tion, a family of countervailing vasodilatory molecules are activated, including the atrial and brain natriuretic peptides (ANP and BNP), bradykinin, prostaglandins (PGE 2 and PGI 2 ), and nitric oxide (NO), that offset the excessive peripheral vascular vasoconstriction. Many of these vasodilatory peptides, including bradykinin and natriuretic peptides, are degraded by a neprilysin, which is a membrane-bound peptidase. These compensatory mechanisms are able to modulate LV function within a physiologic/homeostatic range so that the functional capacity of the patient is preserved or is minimally depressed. Thus, patients may remain asymptomatic or minimally symptomatic for a period of years; however, at some point patients become overtly symp- tomatic, with a resultant striking increase in morbidity and mortality rates.