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

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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–1Nω-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.

Keywords: D-NAME; L-NAME; fetal liver kinase-1 receptor; fms-like tyrosine kinase-1 receptor; vascular endothelial growth factor (VEGF)

Document Type: Research Article


Affiliations: Department of Medicine, University of California San Diego, La Jolla, CA, USA

Publication date: July 1, 2002


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