Hori M, Kitakaze M
First Department of Medicine, Osaka University School of Medicine, Japan.
Hypertension. 1991 Nov;18(5):565-74. doi: 10.1161/01.hyp.18.5.565.
Adenosine is known to regulate myocardial and coronary circulatory functions. Adenosine not only dilates coronary vessels, but attenuates beta-adrenergic receptor-mediated increases in myocardial contractility and depresses both sinoatrial and atrioventricular node activities. The effects of adenosine are mediated by two distinct receptors (i.e., A1 and A2 receptors). A1 adenosine receptors, located in atrial and ventricular myocardium and sinoatrial/atrioventricular nodes, are responsible for inhibition of adenylyl cyclase activity. A2 adenosine receptors, located in coronary endothelial and smooth muscle cells, are responsible for stimulation of this enzyme activity. During increased myocardial oxygen demand due to rapid pacing and exercise, although both coronary blood flow and adenosine concentrations in the myocardium and coronary efflux increased, there is no clear consensus explaining its cause and effect relation at present. However, ischemia/reperfusion-induced coronary hyperemia is believed to be mostly attributed to released adenosine, and it has been proven that adenosine attenuates the severity of ischemia due to its coronary vasodilatory action. The beneficial effects of adenosine during ischemia/reperfusion processes do not seem simple. This is because myocardial ischemia and reperfusion injury is caused by 1) activated leukocytes and platelets, 2) ATP depletion and calcium overload of myocardium, and 3) catecholamine release from the presynaptic nerves as well as 4) the impaired coronary circulation. Intriguingly adenosine attenuates all of these deleterious actions and thereby attenuates ischemia/reperfusion injury. Indeed, adenosine attenuates the severity of contractile dysfunction (myocardial stunning) and limits the infarct size. Thus, administration of adenosine or potentiators of adenosine production in the ischemic myocardium may be beneficial for the attenuation of ischemic and reperfusion injuries, although further clinical investigations are necessary.
已知腺苷可调节心肌和冠状动脉循环功能。腺苷不仅能扩张冠状动脉血管，还能减弱β-肾上腺素能受体介导的心肌收缩力增加，并抑制窦房结和房室结的活动。腺苷的作用由两种不同的受体（即A1和A2受体）介导。A1腺苷受体位于心房和心室心肌以及窦房结/房室结，负责抑制腺苷酸环化酶活性。A2腺苷受体位于冠状动脉内皮和平滑肌细胞，负责刺激该酶的活性。在快速起搏和运动导致心肌需氧量增加期间，尽管冠状动脉血流量以及心肌和冠状动脉流出液中的腺苷浓度均升高，但目前对于其因果关系尚无明确的共识解释。然而，缺血/再灌注诱导的冠状动脉充血被认为主要归因于释放的腺苷，并且已经证明腺苷因其冠状动脉舒张作用而减轻了缺血的严重程度。腺苷在缺血/再灌注过程中的有益作用似乎并不简单。这是因为心肌缺血和再灌注损伤是由1）活化的白细胞和血小板、2）心肌ATP耗竭和钙超载、3）突触前神经释放的儿茶酚胺以及4）受损的冠状动脉循环引起的。有趣的是，腺苷减弱了所有这些有害作用，从而减轻了缺血/再灌注损伤。事实上，腺苷减轻了收缩功能障碍（心肌顿抑）的严重程度并限制了梗死面积。因此，在缺血心肌中给予腺苷或增强腺苷生成的药物可能有助于减轻缺血和再灌注损伤，尽管还需要进一步的临床研究。
