Exercise stimulates neovascularization in occluded muscle without affecting bFGF content

Purpose: This study was conducted to determine whether exercise-induced improvements in capillarity in muscle with peripheral arterial insufficiency (PAI) was accompanied by endothelial cell mitosis, and whether that response could be explained by changes in the expression of basic fibroblast growth factor (bFGF), a known mitogen. Methods: After bilateral ligation of femoral arteries, Sprague-Dawley rats either remained sedentary or participated in a treadmill running protocol. Running time to exhaustion at each session was recorded. On days 1, 2, 3, 5, and 7 of the experimental period, trained-ligated and sedentary-ligated animals were euthanized, and segments of muscle from the gastrocnemius were obtained. Capillarity was determined with histochemistry, and endothelial cell mitotic activity (cell proliferation) was assayed via nuclear uptake of 5'-bromo-2'-deoxyuridine (BrdU), an analog of thymidine. Content of endogenous bFGF was assessed with immunoblotting techniques. Results: Exercise training resulted in augmented function of PAI affected muscle as evidenced by a nearly threefold increase in running time until exhaustion. Trained-ligated muscle demonstrated significantly (P < 0.05) greater capillarity than sedentary-ligated muscle. Vascular remodeling elicited by exercise included the formation of new capillaries (angiogenesis) as indicated by enhanced endothelial cell proliferation at days 3, 5, and 7 of the study. However, exercise training did not alter the content of bFGF in occluded muscle. Conclusion: In muscle with PAI,, exercise training improved functional capacity and capillarity. Angiogenesis was confirmed by the increased mitotic activity of endothelial cells. However, the content of bFGF, a potent angiogenic factor, was not altered. Thus, exercise-induced angiogenesis in PAI affected muscle is not dependent upon increased expression of endogenous bFGF.