Effects of submaximal exercise on monocyte-endothelial interaction in hypercholesterolemic mice

Exercise has been shown to induce nitric oxide synthase. We have found that endothelium-derived nitric oxide (EDNO) is a potent inhibitor of monocyte adherence to the endothelium. Accordingly, this study was designed to test the hypothesis that short-term exercise (11 days) would increase EDNO activity and inhibit monocyte adherence. Male C57BL/6 mice (n=16) were equally divided into 4 groups: a) normal chow (5% fat), b) normal chow plus treadmill exercise (2×1 hour/day, 18m/min, 8' incline), c) atherogenic diet (15% fat), and d) atherogenic diet plus treadmill exercise. Animals were sacrificed immediately after exercise, and aortic tissue and blood were harvested. Atherogenic diet led to a two-fold increase in total cholesterol in both sedentary and exercising mice. Thoracic aortas were opened longitudinally, exposed to medium containing fluorescently labeled mouse monocytoid cells (WEHI 78/24), and counted by epifkiorescent microscopy. Monocytoid cell binding was significantly increased in sedentary mice on atherogenic diet as compared to mice on normal diet (p<0.003). After 11 days of exercise, monocyte binding in hypercholesterolemic mice was significantly reduced (p<0.01) to levels found In mice on normal chow. EDNO elaboration by aortic segments was measured by chemiluminescence and tended to be reduced in sedentary mice on the atherogenic diet, whereas EDNO elaboration In aortic segments from exercising mice on atherogenic diet were not different from those of mice on normal chow. In conclusion, hyperchotesterolemia enhances monocyte binding. This atherogenic effect is completely reversed by daily treadmill exercise. The salutary effect of exercise on endothelial adhesiveness for monocytes may be mediated by NO.