Short-term regular aerobic exercise reduces oxidative stress produced by acute high intraluminal pressure in the adipose microvasculature

Abstract

High blood pressure has been shown to elicit impaired dilation in the vasculature. The purpose of this investigation was to elucidate the mechanisms through which high pressure may elicit vascular dysfunction and determine the mechanisms through which regular aerobic exercise protects arteries against high pressure. Male C57BL/6J mice were subjected to 2 wk of voluntary running (~6 km/day) for comparison with sedentary controls. Hindlimb adipose resistance arteries were dissected from mice for measurements of flow-induced dilation (FID; with or without high intraluminal pressure exposure) or protein expression of NADPH oxidase II (NOX II) and superoxide dismutase (SOD). Microvascular endothelial cells were subjected to high physiological laminar shear stress (20 dyn/cm) or static condition and treated with ANG II + pharmacological inhibitors. Cells were analyzed for the detection of ROS or collected for Western blot determination of NOX II and SOD. Resistance arteries from exercised mice demonstrated preserved FID after high pressure exposure, whereas FID was impaired in control mouse arteries. Inhibition of ANG II or NOX II restored impaired FID in control mouse arteries. High pressure increased superoxide levels in control mouse arteries but not in exercise mouse arteries, which exhibited greater ability to convert superoxide to HO Arteries from exercised mice exhibited less NOX II protein expression, more SOD isoform expression, and less sensitivity to ANG II. Endothelial cells subjected to laminar shear stress exhibited less NOX II subunit expression. In conclusion, aerobic exercise prevents high pressure-induced vascular dysfunction through an improved redox environment in the adipose microvasculature. We describe potential mechanisms contributing to aerobic exercise-conferred protection against high intravascular pressure. Subcutaneous adipose microvessels from exercise mice express less NADPH oxidase (NOX) II and more superoxide dismutase (SOD) and demonstrate less sensitivity to ANG II. In microvascular endothelial cells, shear stress reduced NOX II but did not influence SOD expression.

Regular Aerobic, Resistance, and Cross-Training Exercise Prevents Reduced Vascular Function Following a High Sugar or High Fat Mixed Meal in Young Healthy Adults

“…In conjunction with other studies showing that impaired endothelium function after a high sugar or high fat meal can be prevented by antioxidant treatment, our current findings support the notion that postprandial glycemia and lipemia reduce NO bioavailability in sedentary adults through an increase in oxidative stress (Plotnick et al, 1997 ; Title et al, 2000 ; Beckman et al, 2001 ; Xiang et al, 2008 ). Regular exercise may serve as a potent stimulus that results in adaptations that prevent such occurrences, such as improving insulin sensitivity and up-regulating endogenous anti-oxidant expression and/or activation (Rush et al, 2000 ; Robinson et al, 2017 , 2018 ). Previous studies indicate that even short term inactivity can result in impaired FMD and insulin resistance (Hamburg et al, 2007 ; Boyle et al, 2013 ), while numerous studies indicate exercise improves insulin sensitivity (Borghouts and Keizer, 2000 ).…”

Hypercholesterolemia‐Induced Loss of Flow‐Induced Vasodilation and Lesion Formation in Apolipoprotein E–Deficient Mice Critically Depend on Inwardly Rectifying K + Channels

“…The effects of Ba 2+ (3×10 −5 mol/L), L‐N G ‐Nitroarginine methyl ester (LNAME; 10 −4 mol/L), and apamin (2×10 −8 mol/L) were observed by adding the drug(s) to the circulating bath solution for 30 minutes before repeating the FIV protocol. Administering intraluminal flow in this way effectively isolates the effects of flow‐induced shear stress by keeping intraluminal pressure constant . Performing these experiments in this way fit into the physiological ranges of shear stress arteries of this size experience (≈10 and 50 dynes/cm 2 at pressure gradient–induced flows between Δ40 and Δ100) .…”

“…24 Performing these experiments in this way fit into the physiological ranges of shear stress arteries of this size experience (%10 and 50 dynes/cm 2 at pressure gradient-induced flows between D40 and D100). 3,24 At the end of each protocol, papaverine (10 À4 mol/L) was added to the bath to ensure intact arterial smooth muscle function before proceeding to the next protocol for the same vessel. For arteries that did not dilate to papaverine beyond 80% baseline diameter, especially in the case of experimental groups that exhibited reduced FIV, the experiment was stopped and no measurements were accepted for such an artery as to not include data that may not represent pure endothelial dysfunction in these mouse models.…”

Tetrahydrobiopterin Restores Microvascular Dysfunction in Young Adult Binge Drinkers

“…Using previously described methods, microvascular function was determined by FID in isolated adipose arterioles (Bian et al, ; Robinson et al, ). Briefly, after a 12‐hour fast and abstinence of caffeine, alcohol, and medication use, a gluteal subcutaneous adipose biopsy was obtained from participants.…”

“…Isolated arterioles were cannulated with glass micropipettes and pressurized (60 cm H 2 O or 44 mmHg) in an organ perfusion chamber (37°C) circulated with KREBS solution (pH ~ 7.40) bubbled with air (5% CO 2 and 21% O 2 ) by a peristaltic pump for at least 30 minutes. Lumen diameters were measured by a video microscopy and image measurement system calibrated for horizontal measurements (model VIA‐100; Boeckeler) during responses to flow (pressure gradients of Δ10 to Δ100 cm H 2 O) before and after high intraluminal pressure (150 cm H 2 O or 110 mm Hg) (Robinson et al, ) in the presence or absence of BH 4 (10 −5 M).…”