Abstract :
Recent studies have established the existence of a natriuretic peptide system (NPS) which includes atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptides. In addition to myocardial cell production where the NPS may have autocrine and paracrine actions in the control of myocardial cell growth and contraction, the natriuretic peptides ANP and CNP are also synthesized by the endothelium and mediate arterial and venorelaxation via activation of particulate guanylyl cyclase-linked receptors and potassium channels with additional anti-mitogenic actions. Moreover, this “vascular” natriuretic peptide system may have important “cross-talk” with other endothelial-derived vasodilating and vasoconstricting substances such as nitric oxide and endothelin. CNP production has also been demonstrated in renal epithelial cells but its role in the kidney remains to be defined. The use of a novel natriuretic peptide receptor antagonist nonetheless has recently underscored a functional role for these endogenous peptides in the regulation of sodium excretion, the renin-angiotensin system and arterial pressure in the absence and/or presence of cardiorenal disease states in which the NPS is activated. In such cardiorenal disease states, the plasma elevation of ANP and BNP has permitted their use as sensitive serum markers in the diagnosis of cardiac volume-pressure overload and ventricular hypertrophy. Based upon the biological actions of the NPS and the deleterious myocardial, renal and vascular actions of angiotensin II (ANG II) excess, the dual inhibition of the ectoenzymes neutral endopeptidase 24.11(NEP) which degrades the NPS and of angiotensin converting enzyme (ACE) has been demonstrated to delay the progression of congestive heart failure, reduce ventricular hypertrophy in genetic hypertension and slow the development of experimental atherosclerosis. In summary, the NPS system continues to emerge as an important biological system whose manipulation may have a significant role in the treatment of cardiovascular diseases.
