Caramelo C, Okada K, Tsai P, Linas S L, Schrier R W
Department of Medicine, University of Colorado School of Medicine, Denver.
Kidney Int. 1990 Jul;38(1):47-54. doi: 10.1038/ki.1990.165.
The non-osmotic release of arginine vasopressin (AVP) is associated with the concomitant activation of the renin-angiotensin and sympathetic nervous systems. In vivo studies suggest that a positive interaction may occur between AVP and angiotensin II (Ang II), and other Ca2+ mobilizing hormones. In the present study, the cellular mechanisms of this interaction between AVP and Ang II in vascular smooth muscle cell (VSMC) were examined. These results support the existence of a positive interaction between AVP and Ang II on Ca2+ mobilization in VSMC. In fact, the challenge of VSMC with combined AVP and Ang II, in a range from 5 x 10(-11) to 10(-8) M, enhanced cytosolic free Ca2+ ([Ca2+]i) and 45Ca2+ efflux in a more than additive manner. This potentiation, which was not dependent of the presence of extracellular calcium, correlated with an increased VSMC shape change. Moreover, the combination of subthreshold doses of AVP and Ang II (5 x 10(-11) M), which do not release Ca2+ alone, evoked a Ca2+ mobilizing response. A subthreshold dose of Ang II also shifted to the left the concentration-response curve of the AVP-mediated 45Ca2+ efflux. Since there were no changes in receptor binding of either hormone by the other hormone and the interaction of the two hormones on the production of inositol phosphatides was additive, the AVP and AII positive interaction on Ca2+ mobilization on VSMC may occur at the level of the intracellular Ca2(+)-releasing mechanism itself. Such an interaction can occur at hormone concentrations below the Ca2+ release threshold and may explain an increased functional response to the combination of pressor hormones compared to that of each hormone alone.
精氨酸加压素（AVP）的非渗透性释放与肾素 - 血管紧张素和交感神经系统的同时激活有关。体内研究表明，AVP与血管紧张素II（Ang II）以及其他可动员钙离子的激素之间可能存在正性相互作用。在本研究中，我们检测了血管平滑肌细胞（VSMC）中AVP与Ang II之间这种相互作用的细胞机制。这些结果支持AVP与Ang II在VSMC的钙离子动员方面存在正性相互作用。事实上，用浓度范围为5×10^(-11)至10^(-8) M的AVP与Ang II联合刺激VSMC，以超过相加的方式增强了胞质游离钙离子（[Ca2+]i）浓度和45Ca2+外流。这种增强作用不依赖细胞外钙的存在，与VSMC形态变化增加相关。此外，单独不能释放钙离子的阈下剂量的AVP与Ang II（5×10^(-11) M）联合使用，可引发钙离子动员反应。阈下剂量的Ang II还使AVP介导的45Ca2+外流的浓度 - 反应曲线向左移动。由于一种激素对另一种激素的受体结合没有影响，且两种激素对肌醇磷脂产生的相互作用是相加的，所以AVP与AII在VSMC钙离子动员上的正性相互作用可能发生在细胞内钙离子释放机制本身的水平。这种相互作用可发生在低于钙离子释放阈值的激素浓度下，这可能解释了与单独使用每种激素相比，加压激素联合使用时功能反应增强的现象。
