Ibuprofen Inhibits Skeletal Muscle Hypertrophy in Rats

SOLTOW, QUINLYN A.; BETTERS, JENNA L.; SELLMAN, JEFF E.; LIRA, VICTOR A.; LONG, JODI H. D.; CRISWELL, DAVID S.

Medicine & Science in Sports & Exercise:
doi: 10.1249/01.mss.0000218142.98704.66
BASIC SCIENCES: Original Investigations
Abstract

Purpose: We sought to determine whether cyclooxygenase (COX) activity is necessary for overload-induced growth of adult rat skeletal muscle, and whether nitric oxide synthase (NOS) activity is involved in upregulation of COX messenger RNA (mRNA) expression in skeletal muscle.

Methods: Unilateral surgical removal of the gastrocnemius and soleus was performed on the right hindlimb of 16 female Sprague-Dawley rats (~230 g) to induce chronic overload (OL) of the plantaris for 14 d, with sham surgeries performed on the contralateral leg as a normally loaded (NL) control. Half of the rats were treated with the nonspecific COX inhibitor, ibuprofen (0.2 mg·mL−1 in drinking water; ~20 mg·kg−1·d−1). In a second experiment, the plantaris was unilaterally overloaded for 5 or 14 d in male rats (~350 g; N = 16 rats per time point) and half of the animals were treated with the NOS inhibitor, L-NAME (0.75 mg·mL−1 in drinking water; ~90 mg·kg−1·d−1).

Results: Ibuprofen treatment inhibited plantaris hypertrophy by approximately 50% (P < 0.05) following 14 d of OL, as did L-NAME treatment (P < 0.05). COX-1 and COX-2 mRNA did not differ between any groups at 5 d. At 14 d, however, L-NAME caused a 30-fold increase in plantaris COX-1 mRNA expression independent of loading condition. Additionally, OL induced a 20-fold increase in COX-2 mRNA expression compared with NL (P < 0.05) at 14 d, without affecting COX-1 mRNA level. L-NAME treatment significantly inhibited OL-induced expression of COX-2 mRNA.

Conclusion: COX activity is important for in vivo muscle hypertrophy, and plantaris overload is associated with NOS activity-dependent COX-2 expression.

Author Information

Center for Exercise Science, University of Florida, Gainesville, FL

Address for correspondence: David Criswell, P.O. Box 118206, Center for Exercise Science, University of Florida, Gainesville, FL 32611; E-mail: dcriswell@hhp.ufl.edu.

Submitted for publication September 2005.

Accepted for publication December 2005.

©2006The American College of Sports Medicine