From the Autonomic Neuroscience Institute, Royal Free and University College Medical School, London, United Kingdom.
Circ Res. 2017 Jan 6;120(1):207-228. doi: 10.1161/CIRCRESAHA.116.309726.
There is nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory-motor nerves, as well as in intracardiac neurons. Centers in the brain control heart activities and vagal cardiovascular reflexes involve purines. Adenine nucleotides and nucleosides act on purinoceptors on cardiomyocytes, AV and SA nodes, cardiac fibroblasts, and coronary blood vessels. Vascular tone is controlled by a dual mechanism. ATP, released from perivascular sympathetic nerves, causes vasoconstriction largely via P2X1 receptors. Endothelial cells release ATP in response to changes in blood flow (via shear stress) or hypoxia, to act on P2 receptors on endothelial cells to produce nitric oxide, endothelium-derived hyperpolarizing factor, or prostaglandins to cause vasodilation. ATP is also released from sensory-motor nerves during antidromic reflex activity, to produce relaxation of some blood vessels. Purinergic signaling is involved in the physiology of erythrocytes, platelets, and leukocytes. ATP is released from erythrocytes and platelets, and purinoceptors and ectonucleotidases are expressed by these cells. P1, P2Y, P2Y, and P2X1 receptors are expressed on platelets, which mediate platelet aggregation and shape change. Long-term (trophic) actions of purine and pyrimidine nucleosides and nucleotides promote migration and proliferation of vascular smooth muscle and endothelial cells via P1 and P2Y receptors during angiogenesis, vessel remodeling during restenosis after angioplasty and atherosclerosis. The involvement of purinergic signaling in cardiovascular pathophysiology and its therapeutic potential are discussed, including heart failure, infarction, arrhythmias, syncope, cardiomyopathy, angina, heart transplantation and coronary bypass grafts, coronary artery disease, diabetic cardiomyopathy, hypertension, ischemia, thrombosis, diabetes mellitus, and migraine.
心脏受神经支配，其递质包括 ATP 等，涉及交感神经、副交感神经和感觉运动神经，以及心脏内神经元。脑内中枢控制心脏活动，迷走心血管反射涉及嘌呤。腺嘌呤核苷酸和核苷作用于心肌细胞、房室结和窦房结、心脏成纤维细胞和冠状血管上的嘌呤受体。血管张力受双重机制调控。来自血管周围交感神经的 ATP 通过 P2X1 受体引起血管收缩。内皮细胞在血流变化（通过切应力）或缺氧时释放 ATP，作用于内皮细胞上的 P2 受体，产生一氧化氮、内皮衍生超极化因子或前列腺素，引起血管舒张。感觉运动神经在反射性活动时也释放 ATP，引起部分血管舒张。嘌呤能信号转导参与红细胞、血小板和白细胞的生理功能。ATP 从红细胞和血小板中释放，这些细胞表达嘌呤受体和核苷酸酶。血小板表达 P1、P2Y、P2Y 和 P2X1 受体，介导血小板聚集和形状改变。嘌呤和嘧啶核苷和核苷酸的长期（营养）作用通过 P1 和 P2Y 受体促进血管平滑肌和内皮细胞的迁移和增殖，参与血管生成、血管成形术后再狭窄和动脉粥样硬化时的血管重塑。讨论了嘌呤能信号转导在心血管病理生理学中的作用及其治疗潜力，包括心力衰竭、梗死、心律失常、晕厥、心肌病、心绞痛、心脏移植和冠状动脉旁路移植、冠状动脉疾病、糖尿病心肌病、高血压、缺血、血栓形成、糖尿病和偏头痛。
