Effects of neuronal nitric oxide synthase inhibition on resting and exercising hindlimb muscle blood flow in the rat
Effects of neuronal nitric oxide synthase inhibition on resting and exercising hindlimb muscle blood flow in the rat
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DOI：
10.1113/jphysiol.2009.183723
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发表时间：
2010-04-15
影响因子：
5.5
通讯作者：
Poole, David C.
中科院分区：
文献类型：
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作者：
Copp, Steven W.;Hirai, Daniel M.;Poole, David C.
内皮型一氧化氮合酶(ENOS)来源的一氧化氮合酶(NO)是肌肉收缩过程中血管控制的重要介质。然而，目前尚不清楚神经元型一氧化氮合酶(NNOS)衍生的NO是否调节健康受试者的组织充血，尤其是在运动中。我们验证了选择性抑制一氧化氮合酶会降低静息和动态平板运动(20mmin-1，10%级)大鼠后肢运动肌(S)、肾脏和内脏器官的血流量和血管传导性(VC)的假说。雄性SD大鼠19只，体重555+/-23g，随机分为安静组(n=9)和运动组(n=10)。动脉注射选择性一氧化氮合酶抑制剂S-甲基-L-硫代瓜氨酸(SMTC2.1+/-0.1mmolkg-1)前后，用放射性标记微球测定血流量和VC。总后肢肌肉血流量(对照组：20+/-2mlmin-1100g-1，SMTC：12+/-2mlmin-1100g-1，P<；0.05)和VC(对照组：0.16+/-0.02mlmin-1100g-1，SMTC：0.09+/-0.01mlmin-1100g-1，P<；0.05)显著减少。此外，血流量和VC绝对减少的程度与后肢个别肌肉或肌肉部分发现的氧化肌肉纤维的比例相关(P<；0.05)。运动时，后肢总血流量(对照组：108+/-7mlmin-1100g-1，SMTC：105+/-8mlmin-1100g-1)和VC(对照组：0.77+/-0.06mlmin-1100g-1；SMTC：0.70+/-0.05mlmin-1100g-1)与对照组无显著差异(P>；0.05)。SMTC减少(P<；0.05)静息和运动时肾脏、肾上腺和肝脏的血流量和VC。这些结果增强了我们对NO介导的循环控制作用的理解，证明了nNOS似乎没有在大鼠运动性肌肉充血反应中起到强制性作用。
Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is an integral mediator of vascular control during muscle contractions. However, it is not known whether neuronal NOS (nNOS)-derived NO regulates tissue hyperaemia in healthy subjects, particularly during exercise. We tested the hypothesis that selective nNOS inhibition would reduce blood flow and vascular conductance (VC) in rat hindlimb locomotor muscle(s), kidneys and splanchnic organs at rest and during dynamic treadmill exercise (20 m min-1, 10% grade). Nineteen male Sprague-Dawley rats (555 +/- 23 g) were assigned to either rest (n = 9) or exercise (n = 10) groups. Blood flow and VC were determined via radiolabelled microspheres before and after the intra-arterial administration of the selective nNOS inhibitor S-methyl-l-thiocitrulline (SMTC, 2.1 +/- 0.1 mu mol kg-1). Total hindlimb muscle blood flow (control: 20 +/- 2 ml min-1 100g-1, SMTC: 12 +/- 2 ml min-1 100g-1, P < 0.05) and VC (control: 0.16 +/- 0.02 ml min-1 100 g-1 mmHg-1, SMTC: 0.09 +/- 0.01 ml min-1 100 g-1 mmHg-1, P < 0.05) were reduced substantially at rest. Moreover, the magnitude of the absolute reduction in blood flow and VC correlated (P < 0.05) with the proportion of oxidative muscle fibres found in the individual muscles or muscle parts of the hindlimb. During exercise, total hindlimb blood flow (control: 108 +/- 7 ml min-1 100 g-1, SMTC: 105 +/- 8 ml min-1 100 g-1) and VC (control: 0.77 +/- 0.06 ml min-1 100g-1 mmHg-1; SMTC: 0.70 +/- 0.05 ml min-1 100g-1 mmHg-1) were not different (P > 0.05) between control and SMTC conditions. SMTC reduced (P < 0.05) blood flow and VC at rest and during exercise in the kidneys, adrenals and liver. These results enhance our understanding of the role of NO-mediated circulatory control by demonstrating that nNOS does not appear to subserve an obligatory role in the exercising muscle hyperaemic response in the rat.