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 [


BACKGROUND
Rest or Exercise; Drug: Saline, 30 mg kg(-1)N(omega)-nitro-L-arginine methyl ester (L-NAME), 300 mg kg(-1) L-NAME or 300 mg kg(-1) D-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 approximately 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.
Gavin
T P
TP
Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Wagner
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PD
D000818:Animals; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D018482:Muscle, Skeletal / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000031:analogs & derivatives / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D005082:Physical Exertion / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D012337:RNA, Ribosomal, 18S; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019001:Nitric Oxide Synthase; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D019331:NG-Nitroarginine Methyl Ester