Physical inactivity causes endothelial dysfunction in healthy young mice.
OBJECTIVE
We sought to determine if physical inactivity affects endothelial function in young healthy individuals.


BACKGROUND
Recent studies have linked exercise training to increased bioavailability of vascular nitric oxide (NO) and to improved endothelial function in patients with cardiovascular disorders. The effects of physical inactivity on normal vascular endothelial function are not known.


METHODS
Healthy young male C57Bl/6 mice living in groups of five in large cages, where they were running, climbing, and fighting during their active cycle, were randomly assigned to stay there or to live alone in small cages where they were predominantly resting. After five and nine weeks citrate synthase activity (a measure of mitochondrial respiratory chain activity), heart weight/body weight ratio, vascular reactivity, and protein expression of endothelial nitric oxide synthase (eNOS) were assessed.


RESULTS
Singularized mice showed a reduction of citrate synthase activity (p < 0.05), of endothelium-dependent vasorelaxation (to 65 +/- 5% of control levels; p < 0.001), and of eNOS protein expression (to 53 +/- 8% of control levels; p < 0.01). In striking contrast, vascular responses to potassium chloride, phenylephrine, and the NO-donor racemic S-nitroso-N-acetylpenicillamine were unchanged. The alterations of vascular eNOS-activity were completely reversible when singularized mice underwent exercise. In mice living in groups, exercise showed only a small effect on aortic eNOS expression.


CONCLUSIONS
In young healthy individuals physical inactivity induces endothelial dysfunction, which is completely reversible by a short period of moderate exercise training. We suggest that physical inactivity, the so-called sedentary lifestyle, increases cardiovascular risk in young healthy individuals by inducing endothelial dysfunction.
Suvorava
Tatsiana
T
Institut fuer Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universitaet, Duesseldorf, Germany.
Lauer
Nadine
N
Kojda
Georg
G
D000109:Acetylcholine / Q000008:administration & dosage; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000503:physiopathology; D002950:Citrate (si)-Synthase / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology*; D006352:Heart Ventricles / Q000201:enzymology / Q000503:physiopathology; D008019:Life Style; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008955:Models, Cardiovascular; D009043:Motor Activity / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000008:administration & dosage
D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D002950:Citrate (si)-Synthase; D000109:Acetylcholine