Acute Exertion Elicits a H ₂ O ₂ -Dependent Vasodilator Mechanism in the Microvasculature of Exercise-Trained but Not Sedentary Adults

Abstract

Brachial artery flow mediated vasodilation in exercise trained (ET) individuals is maintained after a single bout of heavy resistance exercise compared to sedentary (SED) individuals. The purpose of this study was to determine if vasodilation is also maintained in the microcirculation of ET individuals. A total of 51 SED and ET individuals underwent gluteal subcutaneous fat biopsy before and after performing a single bout of leg press exercise. Adipose arterioles were cannulated in an organ bath and vasodilation to acetylcholine was assessed ± the endothelial nitric oxide inhibitor L-NAME, the cyclooxygenase inhibitor indomethacin, or the hydrogen peroxide scavenger PEG-catalase. Separate vessels (isolated from the same groups) were exposed to an intraluminal pressure of 150 mmHg for 30 minutes to mimic the pressor response which occurs with isometric exercise. Vasodilation to acetylcholine was reduced in microvessels from SED subjects after either a single weight lifting session or exposure to increased intraluminal pressure whereas microvessels from ET individuals maintained acetylcholine-mediated vasodilation. Prior to weight lifting, vasodilation of microvessels from ET individuals was reduced in the presence of L-NAME and indomethacin. After weight lifting or exposure to increased intraluminal pressure, PEG-catalase significantly reduced vasodilation while L-NAME and indomethacin had no effect. These results indicate that 1) endothelium-dependent vasodilation in the microvasculature is maintained following heavy resistance exercise in ET individuals but not in SED subjects, and that 2) high pressure alone or during weight lifting may induce a mechanistic switch in the microvasculature to favor hydrogen peroxide as the vasoactive mediator of dilation.

David Gutterman

“…7 But for couch potatoes, a smaller jump in blood pressure during weight lifting impaired endothelial function, reducing NO-mediated dilation. 8 The results were similar in cell culture: microvessels from nonathletes switch from NO to hydrogen peroxide release when pressure increases, mimicking the results for patients with cardiovascular disease. 9 Now, Gutterman and others are working to understand how routine exercise in athletes protects blood vessel function from the deleterious effects of stress.…”

Improved arterial flow-mediated dilation after exertion involves hydrogen peroxide in overweight and obese adults following aerobic exercise training

“…Isolated microvessels (ex vivo) have been used to demonstrate that acute strenuous physical exertion reduces endothelium-dependent vasodilator function in the microcirculation as well [11,12]. Adequate perfusion in the microcirculation is essential for organ and tissue health.…”

“…Impaired microvessel function has been linked to hypertension, obesity, and type 2 diabetes mellitus [13]. Proposed mediators of acute physical exertion-induced arterial dysfunction include transient exposure to hypertension, increased sympathetic nervous activity, and activation of renin-angiotensin-aldosterone system [9,11,14].…”

“…Cross-sectional studies indicate that postexertioninduced conduit artery and microvessel dysfunction does not occur in individuals who exercise regularly [7][8][9]11,15]. It has also been found that preserved microvessel endothelium-dependent vasodilator function, following acute exertion in lean exercisers, is hydrogen peroxide (H 2 O 2 ) dependent, whereas resting dilation is nitric oxide dependent, suggesting vascular adaptations occur with chronic exercise that allow for maintained vasodilator function in times of reduced nitric oxide bioavailability [11].…”

Pulse pressure-dependent cerebrovascular eNOS regulation in mice

“…23 This was confirmed by two studies showing that in rat-isolated coronary arterioles 24 and mesenteric arteries, 22 cellular deformation induced by pressure, stretch and wall shear stress, potentiated the release of NO resulting in dilation, despite an increase in ROS production. However, Gutterman's group recently reported that in pressurized human peripheral arterioles, a severe increase in intravascular pressure for 30 min induced either ex vivo (in static conditions) 25 or in vivo (in pulsatile conditions), 26 promoted endothelial dysfunction evidenced by reduced eNOS-dependent NO activity and excessive ROS production. Therefore, both a lack of pulsatile pressure and its excess are damaging to the endothelium as they both impair NO-dependent dilations.…”