Chronic kidney disease (CKD) patients have an exaggerated increase in blood pressure (BP) during rhythmic (RHG 20%) and static (SHG 30%) handgrip exercise. Nitric Oxide (NO) levels increase during exercise and help prevent excessive hypertension by both increasing vasodilation and reducing sympathetic nerve activity (SNA). Therefore, we hypothesized that tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS), would ameliorate the exaggerated exercise pressor response in CKD patients. In a randomized, double-blinded, placebo-controlled trial, we tested the effects of 12 weeks of sapropterin dihydrochloride (6R-BH4, N=18) versus placebo (N=14), on BP and muscle SNA (MSNA) responses during RHG 20% and SHG 30% in CKD patients. The 6R-BH4 group had a significantly lower systolic blood pressure (SBP, +6±1 vs. +13±2 mm Hg, p=0.002) and mean arterial pressure (MAP) response (+5±1 vs. +10±2 mm Hg, p=0.020) during RHG 20%, and a significantly lower SBP response (+19±3 vs. +28±3 mm Hg, p=0.043) during SHG 30%. Under baseline conditions, there was no significant difference in MSNA responses between the groups; however, when equalizing the BP response during exercise between the groups using nitroprusside, the 6R-BH4 group had a significantly lower MSNA response during RHG 20% (6R-BH4 vs. placebo, +12±1 vs. +21±2 bursts/min, p=0.004), but not during SHG 30%. These findings suggest that 6R-BH4 ameliorates the augmented BP response during RHG 20% and SHG 30% in CKD patients. Reduction in reflex activation of SNA may contribute to the decreased exercise pressor response during RHG 20%, but not during SHG 30% in CKD patients.
- sympathetic nerve activity
- handgrip exercise
- exercise pressor reflex
- Copyright © 2015, American Journal of Physiology - Renal Physiology