Effect of tetrahydrobiopterin and exercise training on endothelium-dependent vasorelaxation in SHR

We examined whether the improvement of impaired NO-dependent vasorelaxation by exercise training could be mediated through a BH4-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 BH4 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 BH4 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 BH4-dependent mechanism in established hypertension.