Gao Zhaohui, Kehoe Valerie, Xing Jihong, Sinoway Lawrence, Li Jianhua
Heart and Vascular Institute, Division of Cardiology, Department of Medicine, H047, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Dr., Hershey, PA 17033, USA.
Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1255-61. doi: 10.1152/ajpheart.01303.2005. Epub 2006 Feb 24.
Static muscle contraction increases ATP release into the muscle interstitial space. Elevated ATP in muscle stimulates thin fiber muscle afferents and increases blood pressure via engagement of purinergic P2X receptors. In addition, ATP activates P2X receptors and enhances cardiovascular responses induced by stimulation of muscle mechanoreceptors. In this study, we examined whether elevated muscle temperature would attenuate and whether reduced temperature would potentiate P2X effects on reflex muscle responses. alpha,beta-Methylene ATP (alpha,beta-MeATP) was injected into the arterial blood supply of hindlimb muscle to stimulate P2X receptors, and muscle stretch was induced to activate mechanically sensitive muscle afferents as alpha,beta-MeATP was injected in 10 anesthetized cats. Femoral arterial injection of alpha,beta-MeATP (1.0 mM) increased mean arterial pressure (MAP) by 35+/-5 (35 degrees C), 26+/-3 (37 degrees C), and 19+/-3 mmHg (39 degrees C; P<0.05 vs. 35 degrees C), respectively. Muscle stretch (2 kg) elevated MAP. The MAP response was significantly enhanced 34% and 36% when alpha,beta-MeATP (0.2 mM) was arterially infused 5 min before muscle stretch at 35 degrees and 37 degrees C, respectively. However, as muscle temperature reached 39 degrees C, the stretch-evoked response was augmented only 6% by alpha,beta-MeATP injection, and the response was significantly attenuated compared with the response with muscle temperature of 35 degrees and 37 degrees C. In addition, we also examined effects of muscle temperature on alpha,beta-MeATP enhancement of the cardiovascular responses to static muscle contraction while the muscles were freely perfused and the circulation to the muscles was occluded. Because muscle temperature was 37 degrees C, arterial injections of alpha,beta-MeATP significantly augmented contraction-evoked MAP response by 49% (freely perfused) and 53% (ischemic condition), respectively. It is noted that this effect was significantly attenuated at a muscle temperature of 39 degrees C. These data indicate that the effect of P2X receptor on reflex muscle response is sensitive to alternations of muscle temperature and that elevated temperature attenuates the response.
静态肌肉收缩会增加三磷酸腺苷(ATP)释放到肌肉间质空间。肌肉中升高的ATP会刺激细纤维肌肉传入神经,并通过嘌呤能P2X受体的作用升高血压。此外,ATP会激活P2X受体,并增强由肌肉机械感受器刺激所诱导的心血管反应。在本研究中,我们检测了肌肉温度升高是否会减弱以及温度降低是否会增强P2X对反射性肌肉反应的影响。将α,β-亚甲基ATP(α,β-MeATP)注入后肢肌肉的动脉血供中以刺激P2X受体,并在向10只麻醉猫注射α,β-MeATP时诱发肌肉拉伸以激活机械敏感的肌肉传入神经。股动脉注射α,β-MeATP(1.0 mM)分别使平均动脉压(MAP)升高35±5(35℃)、26±3(37℃)和19±3 mmHg(39℃;与35℃相比,P<0.05)。肌肉拉伸(2 kg)会升高MAP。当在35℃和37℃分别于肌肉拉伸前5分钟动脉内注入α,β-MeATP(0.2 mM)时,MAP反应分别显著增强34%和36%。然而,当肌肉温度达到39℃时,α,β-MeATP注射仅使拉伸诱发的反应增强6%,并且与肌肉温度为35℃和37℃时的反应相比,该反应显著减弱。此外,我们还检测了在肌肉自由灌注且肌肉循环被阻断时,肌肉温度对α,β-MeATP增强心血管对静态肌肉收缩反应的影响。由于肌肉温度为37℃,动脉注射α,β-MeATP分别使收缩诱发的MAP反应显著增强49%(自由灌注)和53%(缺血状态)。值得注意的是,在肌肉温度为39℃时,这种作用显著减弱。这些数据表明,P2X受体对反射性肌肉反应的作用对肌肉温度的变化敏感,且温度升高会减弱该反应。