European Journal of Applied Physiology

, Volume 111, Issue 8, pp 1929–1938 | Cite as

Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin

  • Fayçal Meziri
  • Delphine Binda
  • Sabeur Touati
  • Maxime Pellegrin
  • Alain Berthelot
  • Rhian M. Touyz
  • Pascal Laurant
Original Article


Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise, rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor, especially with pre-existing cardiovascular risk.


Hypertension Exercise Doping Endothelial dysfunction 



The authors thank Isabelle Jallat and Manuel Gil for technical assistance.

Conflict of interest

The other authors report no conflicts.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Fayçal Meziri
    • 1
    • 4
  • Delphine Binda
    • 2
  • Sabeur Touati
    • 1
  • Maxime Pellegrin
    • 2
  • Alain Berthelot
    • 2
  • Rhian M. Touyz
    • 3
  • Pascal Laurant
    • 1
  1. 1.EA4278 Physiology and Physiopathology of Cardiovascular Adaptations to Exercise, Faculty of SciencesUniversity of AvignonAvignonFrance
  2. 2.EA4267 2SBPUFR SMPBesançonFrance
  3. 3.Kidney Research Centre, Ottawa Health Research InstituteUniversity of OttawaOttawaCanada
  4. 4.EA4278 Physiologie et Physiopathologie des Adaptations Cardiovasculaires et à l’ExercicePôle Sportif et de Recherche UniversitaireAvignonFrance

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