Li Jianhua, Sinoway Lawrence I
Division of Cardiology, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, 17033, USA.
Am J Physiol Heart Circ Physiol. 2002 Dec;283(6):H2636-43. doi: 10.1152/ajpheart.00395.2002.
We examined whether ATP stimulation of P2X purinoceptors would raise blood pressure in decerebrate cats. Femoral arterial injection of the P2X receptor agonist alpha,beta-methylene ATP into the blood supply of the triceps surae muscle induced a dose-dependent increase in arterial blood pressure. The maximal increase in mean arterial pressure (MAP) evoked by 0.1, 0.2, and 0.5 mM alpha,beta-methylene ATP (0.5 ml/min injection rate) was 6.2 +/- 2.5, 22.5 +/- 4.4, and 35.2 +/- 3.9 mmHg, respectively. The P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (2 mM ia) attenuated the increase in MAP elicited by intra-arterial alpha,beta-methylene ATP (0.5 mM), whereas the P2Y receptor antagonist reactive blue 2 (2 mM ia) did not affect the MAP response to alpha,beta-methylene ATP. In a second group of experiments, we tested the hypothesis that ATP acting through P2X receptors would sensitize muscle afferents and, thereby, augment the blood pressure response to muscle stretch. Two kilograms of muscle stretch evoked a 26.5 +/- 4.3 mmHg increase in MAP. This MAP response was enhanced when 2 mM ATP or 0.1 mM alpha,beta-methylene ATP (0.5 ml/min) was arterially infused 10 min before muscle stretch. Furthermore, this effect of ATP on the pressor response to stretch was attenuated by 2 mM pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (P < 0.05) but not by the P1 purinoceptor antagonist 8-(p-sulfophenyl)-theophylline (2 mM). These data indicate that activation of ATP-sensitive P2X receptors evokes a skeletal muscle afferent-mediated pressor response and that ATP at relatively low doses enhances the muscle pressor response to stretch via engagement of P2X receptors.
我们研究了ATP对P2X嘌呤受体的刺激是否会使去脑猫的血压升高。向腓肠肌供血动脉内股动脉注射P2X受体激动剂α,β-亚甲基ATP可引起动脉血压剂量依赖性升高。0.1、0.2和0.5 mM α,β-亚甲基ATP（注射速率0.5 ml/min）诱发的平均动脉压（MAP）最大升高分别为6.2±2.5、22.5±4.4和35.2±3.9 mmHg。P2X受体拮抗剂磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸（2 mM，动脉内注射）减弱了动脉内注射α,β-亚甲基ATP（0.5 mM）引起的MAP升高，而P2Y受体拮抗剂活性蓝2（2 mM，动脉内注射）不影响对α,β-亚甲基ATP的MAP反应。在第二组实验中，我们检验了以下假设：通过P2X受体起作用的ATP会使肌肉传入神经敏感化，从而增强对肌肉拉伸的血压反应。两千克的肌肉拉伸使MAP升高26.5±4.3 mmHg。当在肌肉拉伸前10分钟动脉内注入2 mM ATP或0.1 mM α,β-亚甲基ATP（0.5 ml/min）时，这种MAP反应增强。此外，ATP对拉伸升压反应的这种作用被2 mM磷酸吡哆醛-6-偶氮苯基-2',4'-二磺酸减弱（P<0.05），但未被P1嘌呤受体拮抗剂8-（对磺基苯基）-茶碱（2 mM）减弱。这些数据表明，ATP敏感性P2X受体的激活引发了骨骼肌传入神经介导的升压反应，并且相对低剂量的ATP通过P2X受体的参与增强了对拉伸的肌肉升压反应。
