Role of nitric oxide in the regulation of substrate metabolism in heart failure.

Solid experimental evidence indicates that nitric oxide (NO) inhibits oxygen utilization in vitro and in vivo. The role played by NO in cellular metabolism is likely extended to the control of substrate utilization. Studies performed in normal hearts show that NO inhibits glucose uptake and that a reduced synthesis of NO impairs free fatty acid consumption. Interestingly, we found also that myocardial free fatty acid utilization decreases while glucose consumption is enhanced in end stage heart failure, when cardiac NO production falls dramatically. This phenomenon led us to the hypothesis that the reduced synthesis of NO could be at least in part responsible for myocardial metabolic alterations occurring in severe heart failure. The present review mentions some of the seminal studies that defined the function of NO as metabolic modulator. A particular emphasis is put on available data suggesting a role for NO in the control of cardiac substrate utilization in normal and failing hearts.