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Nitric oxide acts as a signaling molecule that promotes vasodilation, which is crucial for meeting the heart and muscles' increased demand during exercise. Endothelial cells produce NO in response to the higher blood flow and chemical signals during activity. It diffuses into the smooth muscle of nearby vessels and activates guanylate cyclase, raising cGMP levels and causing the muscles to relax. This relaxes the vessels, lowers local resistance, and increases blood flow to active muscles, delivering more oxygen and nutrients and helping remove metabolic byproducts.

This is why it is considered the primary role in exercise physiology. It doesn’t directly increase hematocrit, nor does it primarily inhibit mitochondrial biogenesis. It can affect systemic pressures, but the standout, exercise-relevant effect is the targeted vasodilation that boosts muscle perfusion.