Microvascular Vasodilator Plasticity After Acute Exercise

Abstract

Endothelium-dependent vasodilation is reduced after acute exercise or after high intraluminal pressure in isolated arterioles from sedentary adults but not in arterioles from regular exercisers. The preserved vasodilation in arterioles from exercisers is hydrogen peroxide (H2O2) dependent, whereas resting dilation is nitric oxide (NO) dependent. We hypothesize chronic exercise elicits adaptations allowing for maintained vasodilation when NO bioavailability is reduced.

Figure 1. Divergent dilatory signaling between sedentary individuals and exercisers in response to high pressure

At rest, arterioles from both sedentary individuals and regular aerobic or resistance exercisers exhibit nitric oxide (NO)-dependent vasodilation (left panel). This is supported by several studies demonstrating that this dilation is nearly abolished by the NO synthase (NOS) inhibitor L-N^G-Nitroarginine methyl ester (L-NAME) (4, 5, 7). Following exposure to high intraluminal pressure or acute resistance exercise, arterioles from sedentary individuals demonstrate reduced vasodilation and reduced sensitivity to L-NAME and the H₂O₂ scavenger catalase. In contrast, arterioles from regular aerobic and resistance exercisers demonstrate preserved vasodilation, and an enhanced response to catalase, suggesting a greater reliance on H₂O₂-dependent dilation (4, 5, 7).

Figure 2. Exercise and shear induced vascular adaptations

Aerobic exercise and shear stress result in increased vascular AMPK (16) and SOD, resulting in greater conversion of (O₂⁻) to H₂O₂ (15). By reducing O₂⁻, there is likely a resultant increase NO bioavailability. In addition, some studies have demonstrated an increase in NOS expression (14) which would also result in increased NO. Aerobic exercise has also been shown to reduce NOX II subunit expression which results in less O₂⁻, which theoretically should also yield increased NO bioavailability, as superoxide quenches NO to form peroxynitrite (ONOO⁻) (7, 14)

Figure 3. Cellular microenvironment at rest and during high pressure in the exercise trained vasculature

Activation of local RAS results in increased NOX II activity and subsequent production of O₂⁻. Increased SOD expression allows the exercised vasculature to convert this superoxide to H₂O₂ which can be used for vasodilation when NO bioavailability is reduced. Regular exercise results in several beneficial adaptions to the mitochondria (40, 41). Mitochondrial H₂O₂ appears to play a significant role in this maintained dilation as blockade of SOD I and SOD III does not reduce dilation to same extent as catalase which scavenges H₂O₂ from all three SOD isozymes (7).