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International audience; We examined whether the improvement of impaired NO-dependent vasorelaxation by exercise training could be mediated through a BH(4)-dependent mechanism. Male spontaneously hypertensive rats (SHR, n = 20) and Wistar-Kyoto rats (WKY, n = 20) were trained (Tr) for 9 weeks on a treadmill and compared to age-matched sedentary animals (Sed). Endothelium-dependent vasorelaxation (EDV) was assessed with acetylcholine by measuring isometric tension in rings of femoral artery precontracted with 10(-5) M phenylephrine. EDV was impaired in SHR-Sed as compared to WKY-Sed (p = 0.02). Training alone improved EDV in both WKY (p = 0.01) and SHR (p = 0.0001). Moreover, EDV was not different in trained SHR than in trained WKY (p = 0.934). Pretreatment of rings with L-NAME (50 μM) cancelled the difference in ACh-induced relaxation between all groups, suggesting that NO pathway is involved in these differences. The presence of 10(-5) M BH(4) in the organ bath significantly improved EDV for sedentary SHR (p = 0.030) but not WKY group (p = 0.815). Exercise training turned the beneficial effect of BH(4) on SHR to impairment of ACh-induced vasorelaxation in both SHR-Tr (p = 0.01) and WKY-Tr groups (p = 0.04). These results suggest that beneficial effect of exercise training on endothelial function is due partly to a BH(4)-dependent mechanism in established hypertension.

International audience; BACKGROUND: Moderate physical activity enhances endothelium-dependent vasorelaxation. Whether the frequency of exercise affects endothelial function is unclear. The purpose of this study was to investigate the effects of various frequencies of training on endothelium-dependent vasorelaxation. DESIGN: Male Wistar rats were trained for 8 weeks on a treadmill at various frequencies [1 (Ex1), 3 (Ex3) or 5 days/week (Ex5)] and compared with age-matched sedentary animals (SED). A control group allowed us to assess endothelial function before the exercise protocol. Rings of thoracic aorta were precontracted with phenylephrine. RESULTS: Endothelium-independent relaxation elicited by sodium nitroprusside was similar in all groups. The maximal response elicited by acetylcholine (ACh) was not different between groups, whereas pD2 values (-logEC50, EC50 being the concentration of ACh that elicited 50% of the maximal response) significantly correlated with frequency of training. nitro-L-arginine methyl ester (L-NAME) reduced the relaxation elicited by 10(-7) mol/l ACh or higher in control and all trained groups, and by 10(-6) mol/l ACh or higher in SED group. Indomethacin inhibited the vasodilating response to 10(-7) mol/l ACh or higher in control, SED and Ex1 groups, and to 10(-8) mol/l or more in Ex3 and Ex5 animals. Tetraethylammonium attenuated the response to 10(-6) mol/l ACh or higher in control and SED groups and to 10(-7) mol/l or more in all trained animals. CONCLUSION: This data suggest that decreased ACh-induced vasorelaxation after physical inactivity may result from impairment of endothelial nitric oxide synthase, prostacyclin and endothelium-derived hyperpolarizing factor pathways. This effect is prevented by training in a frequency-dependent manner.

The purpose of this study was to determine whether n-3 PUFA result in an effect on endothelial function that is in addition to that of acute exercise. For 4 weeks, male Sprague–Dawley rats were subjected to a diet based on n-3 PUFA or a standard diet. In each diet group, ten rats were submitted to an acute treadmill exercise while the remaining ten acted as sedentary controls. The running speed was progressively increased until the animals were exhausted. Endothelial function was then assessed by measuring isometric tension in rings of the thoracic aorta. In vessels precontracted with 0·1 μm-phenylephrine, responses to acetylcholine (ACh) were significantly improved following acute exercise in all diet groups. When PUFA supplementation was compared to the standard diet no significant difference was found in response to ACh, either at rest or after an acute exercise. Pretreatment of rings with Nω-nitro-l-arginine methyl esther (50 μm) inhibited the ACh-mediated vasorelaxation in all groups. Response to 10 μm-nifedipine, an L-type Ca2+ channel antagonist, was similarly enhanced after acute exercise in both standard and PUFA diets. Furthermore, response to 0·01 μm-nifedipine was significantly higher after acute exercise only in the PUFA diet. In conclusion, in our ‘healthy’ rat model with ‘normal’ baseline endothelial function, acute exercise improves response to ACh while PUFA supplementation alone or in combination with acute exercise has no effect on endothelium-dependent vasorelaxation. However, PUFA may potentiate the acute exercise effect on smooth muscle cell relaxation via L-type Ca2+ channel modifications.