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 O 2 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 O 2 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 O 2 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. • We summarize the effects of nitrate(NO 3 −)/nitrite(NO 2 −) supplementation on exercise tolerance in healthy subjects and heart failure patients, starting with the impact of greater nitric oxide (NO) bioavailability on muscle perfusive and diffusive O 2 conductance up to the mechanisms by which nitrate supplementation enhances muscle contractile function • We also explore how the positive effects of elevated intramyocyte NO bioavailability combine with NO-induced cytochrome c oxidase inhibition to better distribute O 2 across the myocyte • Finally, we highlight what little is known regarding sex differences in response to NO 3 − supplementation and identify next-step questions in this vital arena. [ABSTRACT FROM AUTHOR]