Vaden S L, Adams H R
Eur J Pharmacol. 1985 Nov 26;118(1-2):131-7. doi: 10.1016/0014-2999(85)90671-5.
The cardiodynamic profile of forskolin, a direct activator of adenylate cyclase, was examined in an isovolumic left ventricular (LV) preparation of coronary-perfused guinea-pig hearts. Forskolin consistently induced concentration-dependent increases in LV systolic pressure development, increases in spontaneous beating frequency and decreases in coronary vascular resistance. However, the forskolin concentration required for one-half of the maximal effect (EC50) for coronary vasodilation (3.8 +/- 0.6 X 10(-8) M, n = 6) was 7- to 10-fold less than the EC50 for positive chronotropy (29.3 +/- 4.6 X 10(-8) M, P less than 0.01) and 17- to 20-fold less than the EC50 for positive inotropy (66.3 +/- 7.4 X 10(-8) M, P less than 0.001). The inotropic response to forskolin was not secondary to the concomitant increase in bearing frequency. Also, the coronary vasodilator response persisted in K+-depolarized non-beating hearts, and therefore did not depend on endogeneous coronary vascular autoregulation secondary to increased myocardial oxygen demand. We conclude that forskolin induces direct pharmacologic effects in ventricular muscle, pacemaker cells and the coronary vasculature, but add that the coronary vasculature is over one order of magnitude more sensitive to forskolin than is ventricular muscle. Perhaps adenylate cyclase systems in the heart exist as different subtypes with different affinity characteristics for forskolin-like drugs.
在冠状动脉灌注豚鼠心脏的等容左心室（LV）标本中，研究了腺苷酸环化酶直接激活剂福斯可林的心脏动力学特征。福斯可林始终能引起左心室收缩压呈浓度依赖性升高、自发搏动频率增加以及冠状动脉血管阻力降低。然而，冠状动脉血管舒张达到最大效应一半时所需的福斯可林浓度（EC50）为（3.8±0.6×10⁻⁸ M，n = 6），比引起正性变时作用的EC50（29.3±4.6×10⁻⁸ M，P＜0.01）低7至10倍，比引起正性变力作用的EC50（66.3±7.4×10⁻⁸ M，P＜0.001）低17至20倍。福斯可林引起的变力反应并非继发于伴随的心率增加。此外，冠状动脉血管舒张反应在钾离子去极化的无搏动心脏中持续存在，因此不依赖于因心肌需氧量增加而继发的内源性冠状动脉血管自身调节。我们得出结论，福斯可林在心室肌、起搏细胞和冠状动脉血管中诱导直接药理作用，但补充一点，冠状动脉血管对福斯可林的敏感性比心室肌高一个数量级以上。也许心脏中的腺苷酸环化酶系统以不同亚型存在，对福斯可林样药物具有不同的亲和力特征。
