Nitric oxide synthase inhibition attenuates the skeletal muscle VEGF mRNA response to exercise

• Published in: Journal of applied physiology (1985) 2000-04, Vol.88 (4), p.1192-1198
• Main Authors: Gavin, Timothy P, Spector, David A, Wagner, Harrieth, Breen, Ellen C, Wagner, Peter D
• Format: Article
• Language: English
• Subjects: Anatomy & physiology; Animals; Endothelial Growth Factors - genetics; Enzyme Inhibitors - pharmacology; Exercise; Female; Fibroblast Growth Factor 2 - genetics; Gene Expression Regulation - drug effects; Lymphokines - genetics; Muscle, Skeletal - enzymology; Muscle, Skeletal - physiology; Muscular system; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Physical Conditioning, Animal; Physical Exertion - physiology; Rats; Rats, Wistar; Rest; RNA, Messenger - genetics; Space life sciences; Stereoisomerism; Transcription, Genetic - drug effects; Transforming Growth Factor beta - genetics; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.2000.88.4.1192

Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623 Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and transforming growth factor- 1 (TGF- 1 ) mRNA increase in rat skeletal muscle in response to a single acute exercise bout. Nitric oxide (NO) is released locally by muscle vascular endothelium and muscle fibers during exercise, contributes to the blood flow response to exercise, and regulates mitochondrial respiration. We hypothesized that a reduction in NO production, via NO synthase inhibition, would demonstrate a link between NO and the VEGF, bFGF, and TGF- 1 gene responses to exercise. To investigate this hypothesis, 9-wk-old female Wistar rats were divided into eight treatment groups ( n = 6 each): 1 ) saline +   rest, 2 ) saline + exercise, 3 ) 30 mg/kg N -nitro- L -arginine methyl ester ( L -NAME, a known NOS inhibitor)   + rest, 4 ) 30 mg/kg L -NAME + exercise, 5 ) 300 mg/kg L -NAME + rest, 6 ) 300 mg/kg L -NAME + exercise, 7 ) 300 mg/kg N -nitro- D -arginine methyl ester ( D -NAME, inactive enantiomer of L -NAME) + rest, and 8 ) 300 mg/kg D -NAME + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10° incline. VEGF, TGF- 1 , and bFGF mRNA from left gastrocnemius were analyzed by quantitative Northern blot. Submaximal exercise for 1 h increased VEGF mRNA 4.2-fold and TGF- 1 mRNA 1.5-fold in untreated rats but did not increase bFGF mRNA. The exercise-induced increase in VEGF mRNA was attenuated ~50% by 30 and 300 mg/kg L -NAME; the TGF- 1 mRNA increase was unaffected by 300 mg/kg L -NAME. In addition, 300   mg/kg D -NAME had no effect on the exercise-induced increase in VEGF mRNA. Administration of 300 mg/kg L -NAME had no effect on bFGF mRNA. These findings suggest that NO is important in the regulation of the VEGF gene response to exercise through increases in VEGF transcription or by increases in the VEGF mRNA half-life. vascular endothelial growth factor; transforming growth factor- 1 ; basic fibroblast growth factor; N -nitro- L -arginine methyl ester; N -nitro- D -arginine methyl ester