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

Details

Serval ID
serval:BIB_2DE4BF247500
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Exercise aggravates cardiovascular risks and mortality in rats with disrupted nitric oxide pathway and treated with recombinant human erythropoietin.
Journal
European Journal of Applied Physiology
Author(s)
Meziri F., Binda D., Touati S., Pellegrin M., Berthelot A., Touyz R.M., Laurant P.
ISSN
1439-6327 (Electronic)
ISSN-L
1439-6319
Publication state
Published
Issued date
2011
Volume
111
Number
8
Pages
1929-1938
Language
english
Notes
Publication types: Evaluation Studies ; Journal ArticlePublication Status: ppublish
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.
Keywords
Animals, Cardiovascular Diseases/etiology, Cardiovascular Diseases/mortality, Down-Regulation/drug effects, Enzyme Inhibitors/pharmacology, Erythropoietin/pharmacology, Humans, Male, Mortality, NG-Nitroarginine Methyl Ester/pharmacology, Nitric Oxide/antagonists & inhibitors, Nitric Oxide/metabolism, Nitric Oxide Synthase/antagonists & inhibitors, Nitric Oxide Synthase/metabolism, Physical Conditioning, Animal/physiology, Rats, Rats, Wistar, Recombinant Proteins/pharmacology, Risk Factors, Signal Transduction/drug effects, Signal Transduction/physiology
Pubmed
Web of science
Create date
17/02/2012 15:46
Last modification date
20/08/2019 13:12
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