Buckwalter John B, Taylor Jessica C, Hamann Jason J, Clifford Philip S
Department of Anesthesiology, Medical College of Wisconsin and Veterans Affairs Medical Center, Milwaukee, WI 53295, USA.
J Appl Physiol (1985). 2004 Jul;97(1):417-23; discussion 416. doi: 10.1152/japplphysiol.01181.2003. Epub 2004 Mar 12.
The production of nitric oxide is the putative mechanism for the attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during exercise. We hypothesized that nitric oxide synthase blockade would eliminate the reduction in alpha-adrenergic-receptor responsiveness in exercising skeletal muscle. Ten mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective alpha(1)-adrenergic agonist (phenylephrine) or the selective alpha(2)-adrenergic agonist (clonidine) was infused as a bolus into the femoral artery catheter at rest and during mild and heavy exercise. Before nitric oxide synthase inhibition with N(G)-nitro-l-arginine methyl ester (l-NAME), intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of -91 +/- 3, -80 +/- 5, and -75 +/- 6% (means +/- SE) at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively. Intra-arterial clonidine reduced vascular conductance by -65 +/- 6, -39 +/- 4, and -30 +/- 3%. After l-NAME, intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of -85 +/- 5, -85 +/- 5, and -84 +/- 5%, whereas clonidine reduced vascular conductance by -67 +/- 5, -45 +/- 3, and -35 +/- 3%, at rest, 3 miles/h, and 6 miles/h and 10% grade. alpha(1)-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, alpha(2)-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity. Whereas the inhibition of nitric oxide production eliminated the exercise-induced attenuation of alpha(1)-adrenergic-receptor responsiveness, the attenuation of alpha(2)-adrenergic-receptor responsiveness was unaffected. These results suggest that the mechanism of exercise sympatholysis is not entirely mediated by the production of nitric oxide.
一氧化氮的产生被认为是运动期间工作肌肉中交感神经血管收缩减弱（交感神经阻滞）的机制。我们假设一氧化氮合酶阻断会消除运动骨骼肌中α-肾上腺素能受体反应性的降低。十只杂种狗被长期植入流量探头于双后肢的髂外动脉以及一根股动脉导管。在静息状态、轻度运动和重度运动期间，将选择性α(1)-肾上腺素能激动剂（去氧肾上腺素）或选择性α(2)-肾上腺素能激动剂（可乐定）作为推注注入股动脉导管。在用N(G)-硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮合酶之前，静息状态、3英里/小时以及6英里/小时且坡度为10%时，动脉内注入去氧肾上腺素分别使血管传导率降低-91±3%、-80±5%和-75±6%（平均值±标准误）。动脉内注入可乐定使血管传导率降低-65±6%、-39±4%和-30±3%。在使用L-NAME后，静息状态、3英里/小时以及6英里/小时且坡度为10%时，动脉内注入去氧肾上腺素使血管传导率降低-85±5%、-85±5%和-84±5%，而可乐定使血管传导率降低-67±5%、-45±3%和-35±3%。在重度运动期间，α(1)-肾上腺素能受体反应性减弱。相比之下，即使在轻度运动强度下，α(2)-肾上腺素能受体反应性也会减弱。虽然一氧化氮产生的抑制消除了运动诱导的α(1)-肾上腺素能受体反应性减弱，但α(2)-肾上腺素能受体反应性的减弱不受影响。这些结果表明，运动性交感神经阻滞的机制并非完全由一氧化氮的产生介导。
