An integrated proposal to explain the epidemic of cardiovascular disease in a developing country - From socioeconomic factors to free radicals

An increase of coronary artery disease has been observed in developing coun tries during the last years. Various factors may explain this accelerated i ncrease. We propose that inappropriate diet and inadequate sanitary infrast ructure may act as triggers to create an imbalance between nitric oxide (NO ) and superoxide (O-2(-)). An increase in the concentrations of oxidized LD L produces both decreased NO and increased O-2(-) endothelial synthesis, by accumulation of asymmetrical N-G-N-G-dimethyl-L-arginine, the endogenous i nhibitor of NO, and by activation of NAD(P)H oxidase. On the other hand, hi gh rates of chronic infection-inflammation, due to inappropriate sanitary e nvironment stimulate higher circulating levels of proinflammatory cytokines . These cytokines also contribute to reduced NO and increased O-2(-) endoth elial production through the same mechanisms of oxidized LDL. The net resul t of this imbalance is an increased generation of peroxynitrate that injure s the endothelium in a proatherogenic, prothrombotic and vasoconstrictive m anner. Copyright (C) 2001 S. Karger AG, Basel.