De Mello W C
Departments of Pharmacology and Anesthesiology, School of Medicine, University of Puerto Rico, San Juan 00936-5067.
Hypertension. 1998 Dec;32(6):976-82. doi: 10.1161/01.hyp.32.6.976.
-The influence of intracellular administration of angiotensin II (Ang II) on the inward calcium current (ICa) was investigated in single myocytes isolated from adult rat ventricle. Comparative studies were also made in ventricular cells of Golden hamsters. The ICa was measured in single cells using the whole-cell voltage clamp configuration. The results indicated that Ang II (10(-8) mmol/L) dialyzed into the rat myocytes reduced the peak ICa by 35+/-5.5% (n=20; P<0.05). Losartan (10(-7) mmol/L) added to the bath did not suppress the effects of Ang II, indicating that the peptide is acting intracellularly. Moreover, the intracellular dialysis of losartan (10(-6) mmol/L) or [Sar1Val5Ala8] Ang II (10(-6) mmol/L) did not change the effect of Ang II. Stimulation of ICa by exogenous cAMP or inhibition of protein kinase C did not alter the effect of Ang II on ICa. Zaprinast (100 micromol/L), an inhibitor of cGMP phosphodiesterase, when added to the bath solution increased appreciably the effect of Ang II on ICa (P<0.05). In ventricular myocytes of Golden hamsters, in which Ang II has a positive inotropic action, the intracellular administration of Ang II (10(-8) mmol/L) increased ICa by 36+/-2.4% (n=20; P>0.05). The effect of the peptide was not altered by the intracellular administration of losartan (10(-6) mmol/L), by [Sar1Val5Ala8] Ang II (10(-6) mmol/L), or by the inhibitor of protein kinase A. The inhibition of protein kinase C, however, prevented the effect of Ang II ICa in the hamster myocytes. The results particularly suggest that the activation of the cardiac renin-angiotensin system regulates ICa and myocardial contractility, an effect that varies with the species.
-研究了成年大鼠心室分离的单个心肌细胞中细胞内给予血管紧张素II（Ang II）对内向钙电流（ICa）的影响。还对金黄地鼠的心室细胞进行了比较研究。使用全细胞电压钳模式在单个细胞中测量ICa。结果表明，透析到大鼠心肌细胞中的Ang II（10^(-8) mmol/L）使ICa峰值降低了35±5.5%（n = 20；P<0.05）。加入浴液中的氯沙坦（10^(-7) mmol/L）并未抑制Ang II的作用，表明该肽在细胞内起作用。此外，氯沙坦（10^(-6) mmol/L）或[Sar1Val5Ala8]Ang II（10^(-6) mmol/L）的细胞内透析并未改变Ang II的作用。外源性cAMP刺激ICa或抑制蛋白激酶C并未改变Ang II对ICa的作用。cGMP磷酸二酯酶抑制剂扎普司特（100 μmol/L）加入浴液中时，显著增强了Ang II对ICa的作用（P<0.05）。在Ang II具有正性肌力作用的金黄地鼠心室肌细胞中，细胞内给予Ang II（10^(-8) mmol/L）使ICa增加了36±2.4%（n = 20；P>0.05）。该肽的作用不受细胞内给予氯沙坦（10^(-6) mmol/L）、[Sar1Val5Ala8]Ang II（10^(-6) mmol/L）或蛋白激酶A抑制剂的影响。然而，抑制蛋白激酶C可阻止Ang II对金黄地鼠心肌细胞ICa的作用。这些结果特别表明，心脏肾素-血管紧张素系统的激活调节ICa和心肌收缩力，且该作用因物种而异。
