Newly discovered biologically active humoral factors derived from the cardiovascular system

Their pathophysiological importance and clinical implications

Abstract

Atrial and brain natriuretic peptides derived from the heart regulate the circulatory system in healthy humans and in patients with heart failure by virtue of their potent renal excretory, vasodilatory, and anti-reninaldosterone properties. The value of enhancing these biologically active properties for the treatment of heart failure has been demonstrated by clinical trials. Measurement of plasma levels of these natriuretic peptides is an important tool in the prediction of long-term survival in patients with heart failure. Nitric oxide derived from the endothelium exerts vasodilatory effects and inhibits vascular smooth muscle cell proliferation and platelet aggregation. Reduced production of nitric oxide may limit the dilation of small arteries supplying nutritive blood flow to muscle during exercise, and may therefore be an important factor in predisposition towards and progression of coronary heart disease. Excessive myocardial nitric oxide production provoked by cytokine-induced nitric oxide synthase may reduce heart muscle contractility and induce cardiac cell damage. It may thus be pathophysiologically related to cardiac systolic dysfunction and ventricular remodeling in some forms of heart failure. Endothelin receptor inhibition in patients with heart failure has been shown to increase cardiac output while reducing the systemic and pulmonary vascular resistance. This suggests that inhibition of the biological effects of the peptide may offer a new strategy for the management of cardiovascular disease. Adrenomedullin is a newly discovered potent vasodilatory peptide with mild diuretic and positive inotropic properties, enhancement of which may potentially be useful for treating hypertension and heart failure. These biological active agents produced from the cardiovascular system are now regarded as important autocrine, paracrine, and circulating factors in the regulation of cardiovascular functions and structural change. It follows that measurement and modulation of their properties may provide new strategies for the treatment and diagnosis of cardiovascular disease.