Exercise training results in several muscle adaptations, one of which is angiogenesis. Acutely, exercise leads to release of nitric oxide, prostacyclin (PGI₂), and adenosine (A) in the skeletal muscles. In this paper, we asked whether any of these locally released vasodilators, as well as other known dilator prostaglandins (PGE₁ and PGE₂), have the potential to increase angiogenic growth factor gene expression in resting skeletal muscle. Seven groups of 5-7 female Wistar rats (age 8-12 wk, weight 250 ± 10 g) were anesthetized and instrumented for carotid artery pressure and electromagnetic femoral artery blood flow measurement. One group acted as control while the other groups each received one of the following six agents by constant arterial infusion (dose in µg/min): A (200), nitroprusside (NP, 4.2), acetylcholine (100), PGE₁ (1.9), PGE₂ (1.7), and PGI₂ (1.7). Each agent reduced peripheral vascular resistance to a similar extent (at least twofold). Densitometric mRNA/18S levels for vascular endothelial growth factor (VEGF) were increased 50% by NP and acetylcholine, were unaffected by PGE₁ and PGE₂, and were reduced 40% by PGI₂. For basic fibroblast growth factor, only PGI₂ had any effect, reducing mRNA/18S ~25%. For transforming growth factor-1, A, NP, and PGE₁ led to reduced mRNA/18S, whereas PGE₂ slightly increased mRNA/18S. For the principal putative angiogenic growth factor, VEGF, these data suggest that naturally secreted vasodilators in contracting skeletal muscle could be involved in regulation of gene expression, namely, nitric oxide in a positive and PGI₂ in a negative direction.

blood flow; angiogenesis; vascular endothelial growth factor; basic fibroblast growth factor; transforming growth factor-1; nitric oxide

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