Faculty of Physical Education and Recreation, University of Alberta, Edmonton, Alberta, Canada.
J Appl Physiol (1985). 2013 Jul 1;115(1):97-106. doi: 10.1152/japplphysiol.00250.2013. Epub 2013 May 2.
Isoform-specific nitric oxide (NO) synthase (NOS) contributions to NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle are incompletely understood. The purpose of the present study was to investigate the role of neuronal NOS (nNOS) in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats. We hypothesized that acute pharmacological inhibition of nNOS would augment sympathetic vasoconstriction in resting and contracting skeletal muscle, demonstrating that nNOS is primarily responsible for NO-mediated inhibition of sympathetic vasoconstriction. Sprague-Dawley rats (n = 13) were anesthetized and instrumented with an indwelling brachial artery catheter, femoral artery flow probe, and lumbar sympathetic chain stimulating electrodes. Triceps surae muscles were stimulated to contract rhythmically at 60% of maximal contractile force. In series 1 (n = 9), the percent change in femoral vascular conductance (%FVC) in response to sympathetic stimulations delivered at 2 and 5 Hz was determined at rest and during muscle contraction before and after selective nNOS blockade with S-methyl-l-thiocitrulline (SMTC, 0.6 mg/kg iv) and subsequent nonselective NOS blockade with N(ω)-nitro-l-arginine methyl ester (l-NAME, 5 mg/kg iv). In series 2 (n = 4), l-NAME was injected first, and then SMTC was injected to determine if the effect of l-NAME on constrictor responses was influenced by selective nNOS inhibition. Sympathetic stimulation decreased FVC at rest (-25 ± 7 and -44 ± 8%FVC at 2 and 5 Hz, respectively) and during contraction (-7 ± 3 and -19 ± 5%FVC at 2 and 5 Hz, respectively). The decrease in FVC in response to sympathetic stimulation was greater in the presence of SMTC at rest (-32 ± 6 and -49 ± 8%FVC at 2 and 5 Hz, respectively) and during contraction (-21 ± 4 and -28 ± 4%FVC at 2 and 5 Hz, respectively). l-NAME further increased (P < 0.05) the sympathetic vasoconstrictor response at rest (-47 ± 4 and -60 ± 6%FVC at 2 and 5 Hz, respectively) and during muscle contraction (-33 ± 3 and -40 ± 6%FVC at 2 and 5 Hz, respectively). The effect of l-NAME was not altered by the order of nNOS inhibition. These data demonstrate that NO derived from nNOS and endothelial NOS contribute to the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle.
同工型特异性一氧化氮合酶 (NOS) 对 resting 和 contracting 骨骼肌中 NO 介导的交感神经血管收缩的抑制作用尚不完全清楚。本研究的目的是探讨神经元型 NOS (nNOS) 在健康大鼠 resting 和 contracting 骨骼肌中对交感神经血管收缩的抑制作用。我们假设急性药理学抑制 nNOS 会增加 resting 和 contracting 骨骼肌中的交感神经血管收缩，这表明 nNOS 主要负责 NO 介导的交感神经血管收缩抑制。将 Sprague-Dawley 大鼠（n = 13）麻醉并插入留置肱动脉导管、股动脉流量探头和腰交感神经链刺激电极。三腿肌以 60%的最大收缩力进行节律性收缩。在系列 1（n = 9）中，在 resting 和肌肉收缩期间，在分别用 S-甲基-L-硫代瓜氨酸（SMTC，0.6mg/kg iv）选择性抑制 nNOS 和随后用 N（ω）-硝基-L-精氨酸甲酯（l-NAME，5mg/kg iv）进行非选择性 NOS 抑制之前，确定 2 和 5Hz 时交感神经刺激引起的股血管传导率（%FVC）的变化。在系列 2（n = 4）中，先注射 l-NAME，然后注射 SMTC，以确定 l-NAME 对收缩反应的影响是否受选择性 nNOS 抑制的影响。交感神经刺激使 FVC 在 resting 时下降（分别为-25 ± 7 和-44 ± 8%FVC）和在 contracting 时下降（分别为-7 ± 3 和-19 ± 5%FVC）。在 resting 时，SMTC 存在时交感神经刺激引起的 FVC 下降更大（分别为-32 ± 6 和-49 ± 8%FVC）和 contracting 时（分别为-21 ± 4 和-28 ± 4%FVC）。l-NAME 进一步增加（P < 0.05）在 resting 时的交感血管收缩反应（分别为-47 ± 4 和-60 ± 6%FVC）和 contracting 时的交感血管收缩反应（分别为-33 ± 3 和-40 ± 6%FVC）。l-NAME 的作用不受 nNOS 抑制顺序的影响。这些数据表明，来自 nNOS 和内皮型 NOS 的 NO 有助于抑制 resting 和 contracting 骨骼肌中的交感神经血管收缩。
