Wang Han-Jun, Pan Yan-Xia, Wang Wei-Zhong, Zucker Irving H, Wang Wei
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198-5850, USA.
J Appl Physiol (1985). 2009 Aug;107(2):450-9. doi: 10.1152/japplphysiol.00262.2009. Epub 2009 Jun 4.
Muscle metabolic by-products during exercise, such as K+, lactic acid, ATP, H+, and phosphate, are well established to be involved in the reflex cardiovascular response to static muscle contraction. However, the role of muscle reactive oxygen species (ROS), a metabolic by-product during muscle contraction, in the exercise pressor reflex (EPR) has not been investigated in detail. In the present study, we evaluated the role of muscle ROS in the EPR in a decerebrate rat model. We hypothesized that muscle NADPH oxidase-derived ROS contributes to sensitization of the EPR. Thus the rise in blood pressure and heart rate in response to a 30-s static contraction induced by electrical stimulation of L4/L5 ventral roots was compared before and after hindlimb arterial infusion of the redox agents: diethyldithiocarbamate, a superoxide dismutase inhibitor; the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (tempol); the free radical scavenger dimethylthiourea; a NADPH oxidase inhibitor, apocynin; and a xanthine oxidase inhibitor, allopurinol. The EPR-induced pressor response was augmented after treatment with diethyldithiocarbamate and was attenuated after treatment with tempol, dimethylthiourea, and apocynin. Treatment with allopurinol did not affect the EPR function. None of the drug's affected the EPR heart rate response. In addition, neither the pressor response to electrical stimulation of the central end of dorsal roots, nor femoral blood flow was affected by any treatment. These data suggest that NADPH oxidase-derived muscle ROS plays an excitatory role in the EPR control of blood pressure.
运动过程中肌肉的代谢副产物，如钾离子、乳酸、三磷酸腺苷、氢离子和磷酸盐，已被充分证实参与了对静态肌肉收缩的反射性心血管反应。然而，肌肉活性氧（ROS）作为肌肉收缩过程中的一种代谢副产物，在运动升压反射（EPR）中的作用尚未得到详细研究。在本研究中，我们在去大脑大鼠模型中评估了肌肉ROS在EPR中的作用。我们假设肌肉烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶衍生的ROS有助于EPR的敏化。因此，在对后肢动脉输注氧化还原试剂前后，比较了通过电刺激L4/L5腹根诱导的30秒静态收缩所引起的血压和心率升高情况。这些氧化还原试剂包括：超氧化物歧化酶抑制剂二乙基二硫代氨基甲酸盐；超氧化物歧化酶模拟物4-羟基-2,2,6,6-四甲基哌啶1-氧基（tempol）；自由基清除剂二甲基硫脲；NADPH氧化酶抑制剂夹竹桃麻素；以及黄嘌呤氧化酶抑制剂别嘌呤醇。用二乙基二硫代氨基甲酸盐处理后，EPR诱导的升压反应增强，而用tempol、二甲基硫脲和夹竹桃麻素处理后反应减弱。用别嘌呤醇处理不影响EPR功能。这些药物均未影响EPR的心率反应。此外，对背根中枢端进行电刺激所引起的升压反应以及股血流量均不受任何处理的影响。这些数据表明，NADPH氧化酶衍生的肌肉ROS在EPR对血压的控制中起兴奋作用。
