Nadler E, Barnea O, Vidne B, Isakov A, Shavit G
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
J Basic Clin Physiol Pharmacol. 1993 Jul-Sep;4(3):229-48. doi: 10.1515/jbcpp.1993.4.3.229.
The effect of acetylcholine on cardiac muscle contractility and hemodynamics was investigated in human atrial strips and in isolated working rat heart. Activation of the muscarinic receptor in the heart muscle is generally known to result in negative chronotropic and inotropic effects. In our study, positive inotropic effects of acetylcholine (ACh) were observed in both human right atrial strips and in the working rat heart. Exposure of the human right atrial strips to ACh (10(-7)-10(-4) M) produced a dose dependent tri-phasic (positive-negative-positive) inotropic effect in approximately 40% of the strips. In muscle strips that exhibited only a negative inotropic effect, a positive response was observed following washout of ACh. Both positive and negative effects were antagonized by atropine. Exposure of the paced working rat heart to ACh (10(-7) - 10(-5) M) resulted in a dose dependent decrease in mean coronary flow followed by depression in cardiac function. When the heart was initially treated with the vasodilator adenosine (2 x 10(-6) M), exposure to ACh (10(-7) - 10(-5) M) had no effect on coronary flow and produced a dose dependent augmentation of all cardiodynamic indices: left ventricular pressure, isovolumic pressure, cardiac output, maximal aortic flow and stroke work. This positive response was antagonized by atropine. Exposure of the rat ventricular strips increased the formation of [3H]phosphoinositide breakdown products (e.g. inositol phosphates IP, IP2, IP3). These observations demonstrate that cholinergic muscarinic stimulation may produce positive inotropic effects in both human and rat cardiac muscle. Furthermore, our results suggest that IP3 may be a mediator in this process.
在人房肌条和离体工作大鼠心脏中研究了乙酰胆碱对心肌收缩力和血流动力学的影响。众所周知，心肌中M胆碱能受体的激活会导致负性变时和变力作用。在我们的研究中，在人右房肌条和工作大鼠心脏中均观察到乙酰胆碱（ACh）的正性变力作用。将人右房肌条暴露于ACh（10⁻⁷ - 10⁻⁴ M）会在约40%的肌条中产生剂量依赖性的三相（正性-负性-正性）变力作用。在仅表现出负性变力作用的肌条中，洗脱ACh后观察到正性反应。正性和负性作用均被阿托品拮抗。将起搏的工作大鼠心脏暴露于ACh（10⁻⁷ - 10⁻⁵ M）会导致平均冠状动脉血流量呈剂量依赖性减少，随后心功能降低。当心脏最初用血管扩张剂腺苷（2×10⁻⁶ M）处理时，暴露于ACh（10⁻⁷ - 10⁻⁵ M）对冠状动脉血流量无影响，并使所有心脏动力学指标：左心室压力、等容压力、心输出量、最大主动脉血流量和搏功呈剂量依赖性增加。这种正性反应被阿托品拮抗。大鼠心室肌条暴露后增加了[³H]磷酸肌醇分解产物（如肌醇磷酸IP、IP₂、IP₃）的形成。这些观察结果表明，胆碱能M胆碱能刺激在人和大鼠心肌中均可产生正性变力作用。此外，我们的结果表明IP₃可能是这一过程中的介质。
