European Journal of Applied Physiology

, Volume 104, Issue 5, pp 795–802 | Cite as

Increased nitric oxide synthase activity and Hsp90 association in skeletal muscle following chronic exercise

  • M. Brennan Harris
  • Brett M. Mitchell
  • Sarika G. Sood
  • R. Clinton Webb
  • Richard C. Venema
Original Article


Exercise training results in dynamic changes in skeletal muscle blood flow and metabolism. Nitric oxide (NO) influences blood flow, oxidative stress, and glucose metabolism. Hsp90 interacts directly with nitric oxide synthases (NOS), increasing NOS activity and altering the balance of superoxide versus NO production. In addition, Hsp90 expression increases in various tissues following exercise. Therefore, we tested the hypothesis that exercise training increases Hsp90 expression as well as Hsp90/NOS association and NOS activity in skeletal muscle. Male, Sprague–Dawley rats were assigned to either a sedentary or exercise trained group (n = 10/group). Exercise training consisted of running on a motorized treadmill for 10 weeks at 30 m/min, 5% grade for 1 h. Western blotting revealed that exercise training resulted in a 1.9 ± 0.1-fold increase in Hsp90 expression in the soleus muscle but no increase in neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase, or endothelial nitric oxide synthase (eNOS). Exercise training also resulted in a 3.4 ± 1.0-fold increase in Hsp90 association with nNOS, a 2.3 ± 0.4-fold increase association with eNOS measured by immunoprecipitation as well as a 1.5 ± 0.3-fold increase in eNOS phosphorylation at Ser-1179. Total NOS activity measured by the rate of conversion of L-[14C]arginine to L-[14C]citrulline was increased by 1.42 ± 0.9 fold in soleus muscle following exercise training compared to controls. In summary, a 10-week treadmill training program in rats results in a significant increase in total NOS activity in the soleus which may be due, in part, to increased NOS interaction with Hsp90 and phosphorylation. This interaction may play a role in altering muscle blood flow and skeletal muscle redox status.


Nitric oxide synthase Exercise Skeletal muscle Hsp90 



This work was supported by a National Institutes of Health Individual National Research Service Award (to M.B. Harris) and National Heart, Lung, and Blood Institute Grant HL-72768 (to R.C. Venema). R.C. Venema is an Established Investigator of the American Heart Association. We would like to thank Jonathan M. Goolsby and Michele A. Blackstone for their technical assistance.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • M. Brennan Harris
    • 1
    • 2
    • 5
  • Brett M. Mitchell
    • 4
  • Sarika G. Sood
    • 1
  • R. Clinton Webb
    • 4
  • Richard C. Venema
    • 1
    • 2
    • 3
  1. 1.Vascular Biology CenterMedical College of GeorgiaAugustaUSA
  2. 2.Department of PediatricsMedical College of GeorgiaAugustaUSA
  3. 3.Department of Pharmacology and ToxicologyMedical College of GeorgiaAugustaUSA
  4. 4.Department of PhysiologyMedical College of GeorgiaAugustaUSA
  5. 5.Department of KinesiologyThe College of William & MaryWilliamsburgUSA

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