Exercise training is a well recognized strategy to improve vascular endothelial function by increasing nitric oxide (NO) signalling pathway. However, in hypertensive subjects, previous studies reported that high intensity aerobic exercise (HT) may no longer improve endothelial function. Consequently, the aim of this work was to investigate, in spontaneously hypertensive rats (SHR), the impact of HT exercise on vascular function and especially on NO pathway.

Rats were divided in 3 groups: WKY, sedentary SHR and SHREx, exercised on a treadmill, 1 hour at 85% of their maximal aerobic velocity, 5 days a week for 6 weeks. Arterial function was evaluated on isolated aortic rings in response to ACh or SNP in presence or not of indomethacin, TRAM 34 and Apamin to avoid the contribution of EDHF and cyclooxygenase on endothelium-dependent vasorelaxation. ENOS expression and activation state (phosphorylation at ser1177) were evaluated by western blot. Total Aortic and eNOS-dependent ROS production were assessed using Electron paramagnetic resonance in presence or not of NAC or tetrahydrobiopterin (BH4).

Although eNOS level and phosphorylation were higher in aorta of SHR exercised rats, no beneficial effects of HT were reported on endothelium and eNOS-dependent vasorelaxation. This result was explained by increased eNOS uncoupling in aorta of SHR-Ex rats. Indeed, HT in SHR rats resulted in increased eNOS-dependent ROS production, which was blunted by the use of the recoupling agent BH4 or by the thiol reducing agent (NAC).

The lack of positive effect of HT on endothelial function in SHR rats was the consequence of altered redox state which contribute to uncouple eNOS, switching it from NO to O2.- generation.