De Mello W C
Department of Pharmacology and Anesthesiology, School of Medicine, San Juan, Puerto Rico.
J Cardiovasc Pharmacol. 1994 Apr;23(4):640-6. doi: 10.1097/00005344-199404000-00018.
The possible influence of an intracellular renin-angiotensin system (RAS) on control of cell communication in heart muscle was investigated in cell pairs isolated from adult rats. Junctional conductance (gj) was measured with two separated voltage-clamp circuits. Intracellular dialysis of angiotensin I (AI 10(-8) M) caused a decrease in gj of 76% (SE +/- 3.4) (p < 0.05) in 7 min. The effect of AI appears to be due mainly to its conversion to AII because enalaprilat (10(-9) M) dialysed into the cell caused an appreciable reduction in the effect of AI. AII (10(-8) M) alone caused a decrease in gj of 60% (SE +/- 3.8) (p < 0.05) in 45 s. The effect of AII on gj was suppressed by previous inhibition of protein kinase C (PKC), but enalaprilat could not alter the effect of the peptide. The results indicate that synthesis of AII inside cardiac myocytes plays an important role in modulation of gj and consequently on propagation of the electrical impulse in heart. The effect of AII on gj was blocked by DuP-753 (10(-9) M) administered intracellularly, whereas (Sar1Val5AlA8) AII also caused a slight decrease (1.97 +/- 0.07%) in gj. These findings indicate that an intracellular receptor is involved in the effect of the peptide on gj.
在从成年大鼠分离的细胞对中，研究了细胞内肾素 - 血管紧张素系统（RAS）对心肌细胞间通讯控制的可能影响。用两个分开的电压钳电路测量连接电导（gj）。细胞内透析血管紧张素I（AI 10(-8) M）在7分钟内使gj降低76%（标准误±3.4）（p < 0.05）。AI的作用似乎主要归因于其转化为AII，因为透析到细胞内的依那普利拉（10(-9) M）使AI的作用明显降低。单独的AII（10(-8) M）在45秒内使gj降低60%（标准误±3.8）（p < 0.05）。AII对gj的作用被预先抑制蛋白激酶C（PKC）所抑制，但依那普利拉不能改变该肽的作用。结果表明，心肌细胞内AII的合成在gj的调节中起重要作用，从而对心脏电冲动的传播起重要作用。细胞内给予DuP - 753（10(-9) M）可阻断AII对gj的作用，而（Sar1Val5AlA8）AII也使gj略有降低（1.97±0.07%）。这些发现表明，一种细胞内受体参与了该肽对gj的作用。
