Adaptive and Maladaptive Processes

Aging, hypertension, and coronary artery disease are the major risk factors for congestive heart failure, which is characterized by decreased cardiac output and increased peripheral vascular resistance.Various neurohumoral mechanisms contribute to this phenomenon, among them an increased activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and increased levels of vasopressin. Recently, it has been recognized that substances derived from endothelial cells take part in the regulation of vascular tone. Nitric oxide (NO) formed from l-arginine is the endogenous nitrovasodilator, which is released under basal conditions and in response to shear forces, autacoids, local hormones, neurohumoral mediators, and platelet-derived products. In addition, the endothelium is a source of contracting factors such as endothelin-1, cyclooxygenase products, and, possibly, angiotensin II. The release of NO decreases with age, whereas the production of endothelin-1 remains stable or increases. Hypertension is associated with a decreased basal and stimulated formation of NO, whereas the role of endothelin is still uncertain. In experimental and human congestive heart failure, the vasodilator effects of acetylcholine are attenuated. Basal formation of NO may be increased or reduced depending on the experimental model and conditions used. The circulating levels of endothelin are markedly increased in cardiogenic shock but also in patients and in animal models of heart failure, which could contribute to the increased peripheral vascular resistance in heart failure. Thus, alterations in endothelium-dependent vascular regulation appear to occur in experimental and clinical congestive heart failure. Although the stimulation of the endothelial l-arginine pathway by acetylcholine is blunted, the production of the potent vasoconstrictor endothelin is augmented. These alterations in endothelial function could contribute to the changes of the peripheral circulation in congestive heart failure. (Circulation 1993;87(suppl VII):VII-97-VII-103)