Attenuation of the exercise‐induced increase in skeletal muscle Flt‐1 mRNA by nitric oxide synthase inhibition

We investigated the vascular endothelial growth factor (VEGF) receptor fms‐like‐tyrosine kinase (Flt‐1 and fetal liver kinase‐1 (Flk‐1)] response to acute exercise. In female Wistar rats, the VEGF receptor messenger RNA (mRNA) response to a single acute exercise bout was examined using semi‐quantitative Northern blot from the left gastrocnemius muscles at rest and post‐exercise at 0, 1, 2, 4, 8, 16, 24 and 48 h. Exercise altered both Flt‐1 and Flk‐1 mRNA, with significant increases in Flt‐1 mRNA at 1 and 24 h. However, post‐hoc analysis was unable to discern the time point where a significant increase in Flk‐1 mRNA occurred. To investigate the regulation of Flt‐1 mRNA by exercise we examined if nitric oxide synthase (NOS) inhibition alters the Flt‐1 mRNA response. Eight groups Condition: Rest or Exercise; Drug: Saline, 30 mg kg^–1N^ω‐nitro‐L ‐arginine methyl ester (L ‐NAME), 300 mg kg^–1L ‐NAME or 300 mg kg^–1D ‐NAME] were used to determine the effect of NOS inhibition on the Flt‐1 mRNA response to exercise. L ‐NAME, a known NOS inhibitor, attenuated the exercise‐induced increase in Flt‐1 mRNA by ～50%. These findings suggest that: (1) exercise alters Flt‐1 and Flk‐1 gene expression; and (2) NO is important in the regulation of the Flt‐1 gene response to exercise.