Mechanisms of coronary dysfunction in obesity and insulin resistance.

The incidence of obesity and the metabolic syndrome has reached epidemic proportions and alterations in coronary microvascular function could contribute to the increased cardiovascular morbidity and mortality observed in these patients. This review highlights key mechanisms of impaired control of coronary blood flow in the metabolic syndrome. Specifically, coronary endothelial dysfunction, altered neurohumoral control, and the potential roles of smooth muscle ion channels are addressed. Recent studies indicate that alterations in endothelial-dependent vasodilation or endothelial-dependent vasoconstriction contribute little to obesity-induced impairments in coronary vascular control. In contrast, augmented vasoconstriction in response to neurohumoral mediators appears to play a significant role in coronary vascular dysfunction. The authors conclude that coronary dysfunction in the metabolic syndrome is characterized by an imbalance between coronary blood flow and myocardial metabolism that may be mediated by sensitization of vasoconstrictor pathways. Further, they suggest that alterations in smooth muscle ion channels, Ca(2+) handling, and cell signaling may be important mechanisms leading to coronary microvascular dysfunction. Importantly, however, more research is needed to clearly delineate specific mechanisms and identify potential therapeutic targets.