Increased superoxide in heart failure: a biochemical baroreflex gone awry.

Increased peripheral vascular resistance is a hallmark of advanced chronic congestive heart failure (CHF) and contributes to the phenomenon of “increased afterload” that complicates this condition. Multiple factors probably underlie this phenomenon, including increased water and sodium content of the vasculature, increased neurohormonal activation, and intrinsic abnormalities of the vasculature.1 During the past decade, it has also been shown that endothelium-dependent vasodilation is strikingly abnormal in both experimental animals and humans with compromised cardiac function.2,3 Given that endothelial regulation of vasomotion plays a major role in the control of systemic hemodynamics, this phenomenon is probably a major cause of increased systemic vascular resistance and afterload in heart failure. Because endothelial regulation of vascular tone is mediated predominantly by endothelium-derived nitric oxide (NO), numerous studies have examined abnormalities of the L-arginine/NO pathway in heart failure. Two major abnormalities have surfaced as important.