Limberg Jacqueline K, Malterer Katherine R, Mikhail Kellawan J, Schrage William G, Wilkins Brad W, Nicholson Wayne T, Eisenach John H, Joyner Michael J, Curry Timothy B
Department of Anesthesiology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN, 55905, USA.
Department of Kinesiology, University of Wisconsin, Madison, WI, USA.
Eur J Appl Physiol. 2017 Feb;117(2):237-246. doi: 10.1007/s00421-016-3523-7. Epub 2016 Dec 24.
Previous work has shown nitric oxide (NO) contributes to ~15% of the hyperemic response to dynamic exercise in healthy humans. This NO-mediated vasodilation occurs, in part, via increases in intracellular cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase. We sought to examine the effect of phosphodiesterase-5 (PDE-5) inhibition on forearm blood flow (FBF) responses to dynamic handgrip exercise in healthy humans and the role of NO. We hypothesized exercise hyperemia would be augmented by sildenafil citrate (SDF, PDE-5 inhibitor). We further hypothesized any effect of SDF on exercise hyperemia would be abolished with intra-arterial infusion of the NO synthase (NOS) inhibitor L-N-monomethyl arginine (L-NMMA).
FBF (Doppler ultrasound) was assessed at rest and during 5 min of dynamic forearm handgrip exercise at 15% of maximal voluntary contraction under control (saline) conditions and during 3 experimental protocols: (1) oral SDF (n = 10), (2) intra-arterial L-NMMA (n = 20), (3) SDF and L-NMMA (n = 10). FBF responses to intra-arterial sodium nitroprusside (NTP, NO donor) were also assessed.
FBF increased with exercise (p < 0.01). Intra-arterial infusion of L-NMMA resulted in a reduction in exercise hyperemia (17 ± 1 to 15 ± 1 mL/dL/min, p < 0.01). Although the hyperemic response to NTP was augmented by SDF (area under the curve: 41 ± 7 vs 61 ± 11 AU, p < 0.01), there was no effect of SDF on exercise hyperemia (p = 0.33).
Despite improving NTP-mediated vasodilation, oral SDF failed to augment exercise hyperemia in young, healthy adults. These observations reflect a minor contribution of NO and the cGMP pathway during exercise hyperemia in healthy young humans.
先前的研究表明，一氧化氮（NO）在健康人体内对动态运动充血反应的贡献约为15%。这种由NO介导的血管舒张部分是通过细胞内环磷酸鸟苷（cGMP）增加来实现的，而cGMP会被磷酸二酯酶分解代谢。我们试图研究磷酸二酯酶-5（PDE-5）抑制对健康人前臂血流量（FBF）对动态握力运动反应的影响以及NO的作用。我们假设枸橼酸西地那非（SDF，一种PDE-5抑制剂）会增强运动性充血。我们进一步假设，通过动脉内注入一氧化氮合酶（NOS）抑制剂L- N-单甲基精氨酸（L-NMMA），SDF对运动性充血的任何影响都将被消除。
在静息状态下以及在3种实验方案期间，通过多普勒超声评估FBF：在对照（生理盐水）条件下以及在5分钟的动态前臂握力运动期间，运动强度为最大自主收缩的15%；3种实验方案分别为：（1）口服SDF（n = 10），（2）动脉内注入L-NMMA（n = 20），（3）SDF和L-NMMA（n = 10）。还评估了对动脉内注入硝普钠（NTP，一种NO供体）的FBF反应。
运动时FBF增加（p < 0.01）。动脉内注入L-NMMA导致运动性充血减少（从17±1降至15±1 mL/dL/min，p < 0.01）。尽管SDF增强了对NTP的充血反应（曲线下面积：41±7对61±11 AU，p < 0.01），但SDF对运动性充血没有影响（p = 0.33）。
尽管口服SDF改善了NTP介导的血管舒张，但未能增强年轻健康成年人的运动性充血。这些观察结果反映了在健康年轻人体内运动性充血期间，NO和cGMP途径的作用较小。
