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神经元型一氧化氮合酶抑制对大鼠休息和运动后后肢肌肉血流的影响。

Effects of neuronal nitric oxide synthase inhibition on resting and exercising hindlimb muscle blood flow in the rat.

机构信息

Department of Kinesiology, Kansas State University, Manhattan, KS 66506-5802, USA.

出版信息

J Physiol. 2010 Apr 15;588(Pt 8):1321-31. doi: 10.1113/jphysiol.2009.183723. Epub 2010 Feb 22.

DOI:10.1113/jphysiol.2009.183723
PMID:20176629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2872736/
Abstract

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 micromol 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.

摘要

一氧化氮(NO)来源于内皮型一氧化氮合酶(eNOS),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)产生的 NO 是否调节健康受试者的组织充血,尤其是在运动过程中。我们假设选择性 nNOS 抑制剂的应用会降低大鼠后肢运动肌肉、肾脏和内脏器官在休息和动态跑步机运动(20 m min(-1),10%坡度)时的血流和血管传导(VC)。19 只雄性 Sprague-Dawley 大鼠(555 +/- 23 g)被分配到休息组(n = 9)或运动组(n = 10)。在经动脉给予选择性 nNOS 抑制剂 S-甲基-L-硫代瓜氨酸(SMTC,2.1 +/- 0.1 micromol kg(-1))前后,通过放射性标记微球测定血流和 VC。在休息时,总后肢肌肉血流(对照:20 +/- 2 ml min(-1) 100g(-1),SMTC:12 +/- 2 ml min(-1) 100g(-1),P < 0.05)和 VC(对照: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)均显著降低。此外,血流和 VC 的绝对减少幅度与个体肌肉或后肢肌肉部分中发现的氧化肌纤维的比例相关(P < 0.05)。在运动过程中,总后肢血流(对照:108 +/- 7 ml min(-1) 100 g(-1),SMTC:105 +/- 8 ml min(-1) 100 g(-1))和 VC(对照:0.77 +/- 0.06 ml min(-1) 100g(-1) mmHg(-1);SMTC:0.70 +/- 0.05 ml min(-1) 100g(-1) mmHg(-1))在对照和 SMTC 条件下无差异(P > 0.05)。SMTC 降低了休息和运动时肾脏、肾上腺和肝脏的血流和 VC(P < 0.05)。这些结果增强了我们对 NO 介导的循环控制作用的理解,表明 nNOS 在大鼠运动肌肉充血反应中似乎不是必需的。

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