The skeletal muscle capillary supply is an important determinant of maximum exercise capacity, and it is well known that endurance exercise training increases the muscle capillary supply. The muscle capillary supply and exercise-induced angiogenesis are regulated in part by vascular endothelial growth factor (VEGF). VEGF is produced by skeletal muscle cells and can be secreted into the circulation. We investigated whether there are differences in circulating plasma VEGF between sedentary individuals (Sed) and well-trained endurance athletes (ET) at rest or in response to acute exercise. Eight ET men (maximal oxygen consumption: 63.8 +/- 2.3 ml x kg(-1) x min(-1); maximum power output: 409.4 +/- 13.3 W) and eight Sed men (maximal oxygen consumption: 36.3 +/- 2.1 ml x kg(-1) x min(-1); maximum power output: 234.4 +/- 13.3 W) exercised for 1 h at 50% of maximum power output. Antecubital vein plasma was collected at rest and at 0, 2, and 4 h postexercise. Plasma VEGF was measured by ELISA analysis. Acute exercise significantly increased VEGF at 0 and 2 h postexercise in ET subjects but did not increase VEGF at any time point in Sed individuals. There was no difference in VEGF between ET and Sed subjects at any time point. When individual peak postexercise VEGF was analyzed, exercise did increase VEGF independent of training status. In conclusion, exercise can increase plasma VEGF in both ET athletes and Sed men; however, there is considerable variation in the individual time of the peak VEGF response.

Obesity is associated with lower skeletal muscle capillarization and lower insulin sensitivity. Vascular endothelial growth factor (VEGF) is important for the maintenance of the skeletal muscle capillaries. To investigate whether VEGF and VEGF receptor [kinase insert domain-containing receptor (KDR) and Flt-1] expression are lower with obesity, vastus lateralis muscle biopsies were obtained from eight obese and eight lean young sedentary men before and 2 h after a 1-h submaximal aerobic exercise bout for the measurement of VEGF, KDR, Flt-1, and skeletal muscle fiber and capillary characteristics. There were no differences in VEGF or VEGF receptor mRNA at rest between lean and obese muscle. Exercise increased VEGF (10-fold), KDR (3-fold), and Flt-1 (5-fold) mRNA independent of group. There were no differences in VEGF, KDR, or Flt-1 protein between groups. Compared with lean skeletal muscle, the number of capillary contacts per fiber was the same, but lower capillary density (CD), greater muscle cross sectional area, and lower capillary-to-fiber area ratio were observed in both type I and II fibers in obese muscle. Multiple linear regression revealed that 49% of the variance in insulin sensitivity (homeostasis model assessment) could be explained by percentage of body fat (35%) and maximal oxygen uptake per kilogram of fat-free mass (14%). Linear regression revealed significant relationships between maximal oxygen uptake and both CD and capillary-to-fiber perimeter exchange. Although differences may exist in CD and capillary-to-fiber area ratio between lean and obese skeletal muscle, the present results provide evidence that VEGF and VEGF receptor expression are not different between lean and obese muscle.

Epidemiological studies have linked ambient particulate matter (PM) levels to an increased incidence of adverse cardiovascular events. Yet little is definitively known about the mechanisms accounting for the cardiovascular events associated with PM exposure. The goal of this study was to determine the effects of ultrafine (<0.1 microm) PM exposure on ischemia-reperfusion (I/R) injury. ICR mice were exposed to 100 microg of PM or vehicle by intratracheal instillation. Twenty-four hours later, mice were anesthetized with pentobarbital sodium (60 mg/kg), the left anterior descending coronary artery was ligated for 20 min, flow was restored for 2 h, and the resulting myocardial infarct (MI) size was evaluated. PM exposure doubled the relative size of the MI compared with the vehicle control. No difference was observed in the percentage of the left ventricle at risk for ischemia. PM exposure increased the level of oxidative stress in the myocardium after I/R. The density of neutrophils in the reperfused myocardium was increased by PM exposure, but differences in the number of blood leukocytes, expression of adhesion molecules on circulating neutrophils, and activation state of circulating neutrophils 24 h after PM exposure could not be correlated to the increased I/R injury observed. Additionally, aortas isolated from PM-exposed animals and studied in vitro exhibited a reduced endothelium-dependent relaxation response to acetylcholine. These results indicate that exposure to ultrafine PM increases oxidative stress in the myocardium, alters vascular reactivity, and augments injury after I/R in a murine model.

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Objective: Owing to the relationship between nitric oxide related endothelial dysfunction, insulin resistance and cardiovascular disease in overweight individuals, we investigated if skeletal muscle endothelial nitric oxide synthase (eNOS) protein content and activity are lower in overweight than lean women. Design: A total of 19 women (age 26.071.7 years) underwent a resting muscle biopsy, body composition analysis by hydrostatic weighing and peak aerobic capacity determination using indirect calorimetry (Study 1). An additional separate set of six lean (p25% fat) and six overweight (425% fat) women were subsequently studied for the determination of eNOS activity, and to better control for absolute peak aerobic capacity between lean and overweight women (Study 2). Results: Skeletal muscle eNOS content was inversely related to percent body fat (r 2 ¼ 0.58, Po0.01), and body mass index (r 2 ¼ 0.35, Po0.05). Total eNOS activity was lower in overweight than lean women (2.0970.22 vs 1.4470.17 U, Po0.05; n ¼ 12), and was inversely related to percent body fat (r 2 ¼ 0.32, P ¼ 0.05), and BMI (r 2 ¼ 0.41, Po0.05). Absolute and relative aerobic capacity were not independent predictors of skeletal muscle eNOS content (r 2 ¼ 0.11 and 0.26, respectively). Conclusion: There is an inverse relationship between eNOS and percent body fat that may have implications for the previously reported reduced endothelial function and insulin sensitivity in overweight women.