Skeletal Muscle Contractile Function in Heart Failure With Reduced Ejection Fraction—A Focus on Nitric Oxide

FIGURE 1. The main pathways for nitric oxide (NO) production. The dietary pathway (starting at upper left) utilizes NO3 - and is facilitated by lower pO2 and pH. Ingestion of NO3 −-containing foods, especially vegetables such as beetroot, start this pathway. NO3 − is reduced to nitrite (NO2 -) by reductases or acidic conditions and facilitated by oxyheme proteins. Then NO2 - is reduced to NO under the appropriate conditions. Importantly, skeletal muscle can serve as a ‘reservoir’ for nitrate. As shown by the dashed arrows, this pathway can also ‘run in reverse’ with NO being used to create NO2 - and then NO3 − given the appropriate conditions. *Note: NO3 − can be taken up from the circulation into the salivary glands and go through this reduction pathway again in what is known as ‘the enterosalivary pathway.’ The endogenous pathway (lower left) uses NO synthase and oxygen to create citrulline and NO. An abbreviated depiction of the organic nitrate pathway (lower right) shows the production of NO derived from pharmacologic sources, such as nitroglycerin. ALDH-2 = aldehyde dehydrogenase, P450 = cytochrome P450. Reproduced with permission from Biochimica et Biophysica Acta (BBA)—Molecular…

FIGURE 2. Average concentrations of plasma NO3 - and NO2 - observed in patients (N = 5) following a 10 mmol dose of KNO3. NO3 - concentrations are depicted as blue triangles, and NO2 - concentrations as red squares (Reproduced with permission from Pharmacology Research).