This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Suvorava, T. Articles by Kojda, G. Search for Related Content PubMed PubMed Citation Articles by Suvorava, T. Articles by Kojda, G.

Physical inactivity causes endothelial dysfunction in healthy young mice

Institut fuer Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universitaet, Duesseldorf, Germany

Manuscript received March 31, 2004; revised manuscript received May 25, 2004, accepted June 7, 2004.

^* Reprint requests and correspondence: Dr. Georg Kojda, Institut fuer Pharmakologie und Klinische Pharmakologie, Heinrich-Heine-Universitaet, Moorenstr. 5, 40225 Duesseldorf, Germany (Email: kojda{at}uni-duesseldorf.de).

OBJECTIVES: 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.

Abbreviations and Acronyms   ACh = acetylcholine   ANOVA = analysis of variance   eNOS = endothelial nitric oxide synthase   KCl = potassium chloride   NO = nitric oxide   pD2 = half maximal effective concentration in –log mol/l   PE = phenylephrine   SNAP = racemic S-nitroso-N-acetylpenicillamine

This article has been cited by other articles:

				J.-a Kim, Y. Wei, and J. R. Sowers Role of Mitochondrial Dysfunction in Insulin Resistance Circ. Res., February 29, 2008; 102(4): 401 - 414. [Abstract] [Full Text] [PDF]

				N. M. Hamburg, C. J. McMackin, A. L. Huang, S. M. Shenouda, M. E. Widlansky, E. Schulz, N. Gokce, N. B. Ruderman, J. F. Keaney Jr, and J. A. Vita Physical Inactivity Rapidly Induces Insulin Resistance and Microvascular Dysfunction in Healthy Volunteers Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2650 - 2656. [Abstract] [Full Text] [PDF]

				G. Kojda and R. Hambrecht Molecular mechanisms of vascular adaptations to exercise. Physical activity as an effective antioxidant therapy? Cardiovasc Res, August 1, 2005; 67(2): 187 - 197. [Abstract] [Full Text] [PDF]

				N. Lauer, T. Suvorava, U. Ruther, R. Jacob, W. Meyer, D. G. Harrison, and G. Kojda Critical involvement of hydrogen peroxide in exercise-induced up-regulation of endothelial NO synthase Cardiovasc Res, January 1, 2005; 65(1): 254 - 262. [Abstract] [Full Text] [PDF]