NOS inhibition accelerates atherogenesis: reversal by exercise

Area of Science:

• Cardiovascular Research
• Exercise Physiology
• Pharmacology

Background:

• Atherosclerosis is a complex disease influenced by genetic and environmental factors.
• Nitric oxide (NO) plays a crucial role in vascular health and preventing atherosclerosis.
• Hypercholesterolemia is a primary risk factor for developing atherosclerotic lesions.

Purpose of the Study:

• To investigate the impact of chronic exercise on atherosclerotic lesion development in hypercholesterolemic mice.
• To determine if exercise can counteract the pro-atherogenic effects of nitric oxide synthase inhibition.
• To assess the combined effects of exercise and NG-nitro-L-arginine (L-NNA) on cardiovascular endurance and lesion formation.

Main Methods:

• Apolipoprotein E-deficient mice were subjected to 12 weeks of treadmill exercise.
• Mice received oral NG-nitro-L-arginine (L-NNA), a nitric oxide synthase antagonist, or a placebo.
• Atherosclerotic lesion area in the aorta was quantified using oil red O staining.
• Mice endurance was measured by the distance run to exhaustion.

Main Results:

• Mice treated with L-NNA exhibited a threefold increase in aortic atherosclerotic lesion formation compared to control groups.
• Chronic exercise training significantly reduced L-NNA-induced lesion formation.
• Exercise training improved running endurance, particularly in mice receiving L-NNA.
• Sedentary mice treated with L-NNA showed the most pronounced increase in lesion size.

Conclusions:

• Inhibition of nitric oxide synthase with L-NNA accelerates atherogenesis in hypercholesterolemic mice.
• Chronic exercise training effectively counteracts the adverse effects of L-NNA on lesion development.
• Exercise demonstrates a significant protective role against diet- and drug-induced atherosclerosis.