Role of nitric oxide in convective and diffusive skeletal muscle microvascular oxygen kinetics.

Progress in understanding physiological mechanisms often consists of discrete discoveries made across different models and species. Accordingly, understanding the mechanistic bases for how altering nitric oxide (NO) bioavailability impacts exercise tolerance (or not) depends on integrating information from cellular energetics and contractile regulation through microvascular/vascular control of O2 transport and pulmonary gas exchange. This review adopts state-of-the-art concepts including the intramyocyte power grid, the Wagner conflation of perfusive and diffusive O2 conductances, and the Critical Power/Critical Speed model of exercise tolerance to address how altered NO bioavailability may, or may not, affect physical performance. This question is germane from the elite athlete to the recreational exerciser and particularly the burgeoning heart failure (and other clinical) populations for whom elevating O2 transport and/or exercise capacity translates directly to improved life quality and reduced morbidity and mortality. The dearth of studies in females is also highlighted, and areas of uncertainty and questions for future research are identified.