NO and superoxide: Opposite ends of the seesaw in cardiac contractility

摘要

The discovery of superoxide dis-mutase by McCord and Fridov-ich (1) ushered in a new area of biology wherein free radicals had to be factored into the biology of animals and plants. The free radical species of oxygen, the superoxide anion radical, has become the focus of thousands of studies. In medicine, the number of disease processes that have been linked to overexposure to oxidants or a failure to defend against them is vast, including pathologies as diverse as neu-rodegeneration, sepsis, atherosclerosis, and arthritis. The NO free radical and its redox partners, the nitrosonium and nitroxide ions, have been similarly painted with broad negative brushes (2). More recently, NO has been recognized for its role in normal physiology, arising in part from its ability to act as a signal through regulation of guanylate cyclase (3) and to S-nitrosylate cysteinyl residues of proteins and peptides (3). In a recent issue of PNAS, we witnessed the emergence of a new paradigm wherein the interplay between different highly reactive species allows for complex and fast regulation of cellular processes whose disruption has potentially serious pathological consequences (4).