We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin.
- Authors
Meziri, Fayçal; Binda, Delphine; Touati, Sabeur; Pellegrin, Maxime; Berthelot, Alain; Touyz, Rhian M.; Laurant, Pascal; Meziri, Fayçal
- Abstract
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.
- Subjects
RECOMBINANT erythropoietin; HYPERTENSION risk factors; DOPING in sports; NITRIC oxide; LABORATORY rats; CARDIOVASCULAR disease related mortality; ANIMAL experimentation; ARGININE; BIOCHEMISTRY; CARDIOVASCULAR diseases; CELLULAR signal transduction; COMPARATIVE studies; ENZYME inhibitors; ERYTHROPOIETIN; PHENOMENOLOGY; RESEARCH methodology; MEDICAL cooperation; MORTALITY; OXIDOREDUCTASES; PHYSICAL fitness; RATS; RECOMBINANT proteins; RESEARCH; EVALUATION research; CHEMICAL inhibitors; PHARMACODYNAMICS
- Publication
European Journal of Applied Physiology, 2011, Vol 111, Issue 8, p1929
- ISSN
1439-6319
- Publication type
journal article
- DOI
10.1007/s00421-011-1829-z