Voluntary physical activity alterations in endothelial nitric oxide synthase knockout mice

Area of Science:

• Physiology
• Molecular Biology
• Exercise Science

Background:

• Endothelial nitric oxide synthase (eNOS) regulates vasoreactivity and angiogenesis.
• Previous research indicated eNOS deficiency reduces mitochondrial oxidative capacity in slow-twitch skeletal muscle.
• The role of eNOS in exercise adaptation and muscle energy metabolism requires further investigation.

Purpose of the Study:

• To investigate the role of eNOS in physical activity and exercise-induced adaptations in muscle energy metabolism.
• To compare the physical capacity and exercise response between eNOS knockout (eNOS-/-) and wild-type (WT) mice.
• To analyze the impact of voluntary exercise on enzyme profiles in cardiac, soleus (Sol), and gastrocnemius (Gast) muscles.

Main Methods:

• An 8-week voluntary wheel-running protocol was used to assess physical capacity in eNOS-/- and WT mice.
• Energy metabolism enzyme profiles (cytochrome-c oxidase, citrate synthase, creatine kinase) were measured in cardiac, Sol, and Gast muscles.
• Muscle weight and running performance parameters (distance, speed) were analyzed.

Main Results:

• eNOS-/- mice exhibited significantly lower running distance and maximal speed compared to WT mice.
• Voluntary exercise increased Sol muscle weight in WT mice but not in eNOS-/- mice.
• In eNOS-/- mice, exercise decreased key metabolic enzyme activities (COX, citrate synthase, creatine kinase) in Sol muscle, unlike in WT mice. Cardiac and Gast muscles showed minimal changes.

Conclusions:

• eNOS is essential for maintaining adequate physical capacity and facilitating exercise-induced adaptations in skeletal muscle.
• Downregulation of eNOS can negatively impact energy metabolism in oxidative skeletal muscle, even with moderate physical activity.
• These findings highlight eNOS's critical role in exercise physiology and muscle adaptation.