Chronic hypoxia exposure depresses aortic endothelium-dependent vasorelaxation in both sedentary and trained rats: involvement of L-arginine.
This study was designed to test the hypothesis that the previously demonstrated training-induced improvement of the endothelium vasodilator function would be blunted under conditions of chronic hypoxia exposure as a result of deleterious effects of hypoxia per se on the nitric oxide pathway. Sea-level-native rats were randomly assigned to N (living in normoxia), NT (living and training 5 days/wk for 5 wk in normoxia), CH (living in hypoxia, 2,800 m), and CHT (living and training 5 days/wk for 5 wk in hypoxia, 2,800 m) groups. Concentration-response curves to acetylcholine (ACh; 10(-9) to 10(-4) M) with or without L-arginine (10(-3) to 10(-5) M) and/or nitro-L-arginine methyl ester (10(-5) M) were assessed on aortic isolated rings. The main finding was that chronic hypoxia severely depressed maximal ACh-responses of aortic rings in both sedentary and trained groups. However, chronic hypoxia did not interfere with training-induced increases in maximal ACh responses, considering that maximal ACh vasorelaxation was improved in CHT rats to the same extent as in NT rats when both groups were directly compared with their sedentary counterparts. It should be pointed out that the vasodilator response to ACh was restored in CH and CHT rats to the level obtained in N and NT rats, respectively, by an in vitro L-arginine addition. A hypoxia-induced decrease in L-arginine bioavailability resulting from acclimatization at altitude may be involved in this limitation of the NO pathway in CH and CHT rats. These results are of importance for aerobic performance as the specific vascular adaptations to training at altitude could contribute to limit peripheral vasodilatation and subsequently blood flow during exercise.
Reboul
C
C
Dynamique des Incohérences Cardio-Vasculaires, Faculté des Médecine de Nîmes, Montpellier, France.
Tanguy
S
S
Gibault
A
A
Dauzat
M
M
Obert
P
P
D000222:Adaptation, Physiological; D000532:Altitude Sickness / Q000503:physiopathology*; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001120:Arginine / Q000378:metabolism*; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D009043:Motor Activity; D009569:Nitric Oxide / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000379:methods*; D051381:Rats; D012146:Rest; D014664:Vasodilation
D009569:Nitric Oxide; D001120:Arginine