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Circulation Research. 2002;91:1190-1197
Published online before print November 7, 2002, doi: 10.1161/01.RES.0000046233.94299.D6
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(Circulation Research. 2002;91:1190.)
© 2002 American Heart Association, Inc.


Integrative Physiology

Physical Training Increases eNOS Vascular Expression and Activity and Reduces Restenosis After Balloon Angioplasty or Arterial Stenting in Rats

Ciro Indolfi*, Daniele Torella*, Carmela Coppola, Antonio Curcio, Francisca Rodriguez, Antonio Bilancio, Antonio Leccia, Oreste Arcucci, Mariacristina Falco, Dario Leosco, Massimo Chiariello

From the Division of Cardiology (C.I., A.C.), Magna Græcia University, Catanzaro, Italy; the Divisions of Cardiology (D.T., C.C., A.L., O.A., M. F., M.C.) and Gerontology, (D.L.), Federico II University, Naples, Italy; Genecor Foundation (C.I., D.T.), Naples, Italy; the Department of Pharmacology, New York Medical College (F.R.), Valhalla, NY; and the Department of General Pathology, Second University of Naples (A.B.), Naples, Italy. Present address for A.B. is Ludwig Institute for Cancer Research, London, UK.

Correspondence to Ciro Indolfi, MD, Chief, Division of Cardiology, Magna Græcia University, Via Tommaso Campanella, 115, 88100 Catanzaro, Italy. E-mail indolfi{at}unicz.it

The effects of dynamic exercise on restenosis after vascular injury are still unknown. The consequences of balloon dilation–induced injury on neointimal hyperplasia, vascular negative remodeling, and reendothelialization were assessed in sedentary and trained rats. Ex vivo eNOS vascular expression and activity were investigated in carotid arteries isolated from sedentary and exercised rats. The in vivo effects of eNOS inhibition by L-NMMA on vessel wall after balloon dilation were evaluated in sedentary and exercised rats. We also investigated the effects of exercise on neointimal formation in a rat stent model of vascular injury. Compared with sedentary group, the arteries isolated from trained rats showed higher levels of eNOS protein expression and activity 7 days after balloon dilation. A significant reduction of both neointimal hyperplasia and negative remodeling was observed 14 days after balloon injury in trained compared with sedentary rats. Moreover, we demonstrated that exercise training produced accelerated reendothelialization of the balloon injured arterial segments compared with sedentary. L-NMMA administration eliminated the benefits of physical training on vessel wall after balloon dilation. Finally, a decrease of neointimal hyperplasia as well as of platelet aggregation was observed after stent deployment in trained rats compared with sedentary. In conclusion, physical exercise could favorably affect restenosis after balloon angioplasty and stenting. Increase in eNOS expression and activity might contribute to the potential beneficial effects of exercise on the vessel wall after vascular injury.


Key Words: exercise • restenosis • balloon angioplasty • stent • nitric oxide synthase




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