Natriuretic Peptides—Relevance in Cardiovascular Disease

4In contrast, the increase in intravascular volume from dietary salt loading results in the expected increase in BNP. 4 Similarly, a change in a patient’s pacemaker mode from atrial to ventricular pacing leading to uncoordinated atrial contractions and high pressure waves causes a greater acute increase in plasma ANP than BNP. 5 It therefore appears that BNP level reflects long-term intravascular volume status rather than momentary volume. Moreover, BNP is more stable than ANP in plasma and has a longer half-life, 6 which may be attributable to its lesser affinity for clearance receptors. CNP is synthesized in the endothelium and has vasodilatory and antiproliferative effects on vascular smooth muscle. It has a local action in the blood vessels or within the organ where it is produced. The natriuretic peptides are cleared from the circulation by at least 2 mechanisms. They bind to widely distributed natriuretic peptide clearance receptors (NPR-Cs) on endothelial cells and are then internalized and degraded. 7 They are also metabolized by neutral endopeptidases that are widely distributed on cells of various tissues. 2 Actions Intravenous infusion of ANP or BNP has a potent natriuretic and diuretic effect in healthy subjects, and infusions of supraphysiological concentrations of these peptides also show some hypotensive effect and suppression of the reninangiotensin-aldosterone system. 6,8,9 The effects of ANP and BNP seem to be additive, which may be because ANP and BNP share a common receptor (NPR-A). 6 Activation of this receptor leads to formation of cyclic guanosine monophosphate (cGMP), the second messenger mediating the effects of the natriuretic peptides. Plasma ANP and BNP levels are markedly increased in congestive heart failure, the magnitude of increase being related to the degree of heart failure. 2 Because their actions include vasodilation, natriuresis, and suppression of the renin-angiotensin-aldosterone system, ANP and BNP may be endogenous hormones counteracting the development of heart failure. The physiological effects of exogenous ANP are blunted in patients with congestive heart failure compared with its effects in normal subjects. 9 Proposed explanations for this resistance include receptor down-regulation and increased cGMP phosphodiesterase activity. 2 In contrast, BNP infused intravenously in patients with chronic congestive heart failure leads to a dose-dependent natriuretic response, a decrease in pulmonary capillary wedge pressure, and an increase in cardiac output. 10