INTERACTION OF ARGININE VASOPRESSIN AND ANGIOTENSIN-II ON CA-2+ IN VASCULAR SMOOTH-MUSCLE CELLS

INTERACTION OF ARGININE VASOPRESSIN AND ANGIOTENSIN-II ON CA-2+ IN VASCULAR SMOOTH-MUSCLE CELLS
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DOI:
10.1038/ki.1990.165
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发表时间:
1990-07-01
影响因子:
19.6
通讯作者:
SCHRIER, RW
SCHRIER, RW
中科院分区:
医学1区
文献类型:
--
作者:
CARAMELO, C;OKADA, K;SCHRIER, RW

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精氨酸加压素 (AVP) 的非渗透释放与肾素-血管紧张素和交感神经系统的伴随激活有关。体内研究表明,AVP 和血管紧张素 II (Ang II) 以及其他 Ca2+ 动员激素之间可能会发生积极的相互作用。在本研究中,研究了血管平滑肌细胞(VSMC)中 AVP 和 Ang II 之间相互作用的细胞机制。这些结果支持 AVP 和 Ang II 之间存在对 VSMC 中 Ca2+ 动员的正相互作用。事实上,结合AVP和Ang II对VSMC的挑战在5倍范围内。 10-11 至 10-8 M,以超过相加的方式增强胞质游离 Ca2+ ([Ca2+]i) 和 45Ca2+ 流出。这种增强作用不依赖于细胞外钙的存在,与 VSMC 形状变化的增加相关。此外,AVP和Ang II的阈下剂量的组合(5×10-11M)不会单独释放Ca 2+ ,但会引起Ca 2+ 动员反应。阈下剂量的 Ang II 也使 AVP 介导的 45Ca2+ 流出的浓度反应曲线向左移动。由于两种激素与另一种激素的受体结合没有变化,并且两种激素对肌醇磷脂产生的相互作用是相加的,因此 AVP 和 AII 对 VSMC 上 Ca2+ 动员的正相互作用可能发生在细胞内 Ca2+ 释放机制本身的水平上。这种相互作用可以在激素浓度低于 Ca2+ 释放阈值时发生,并且可以解释与单独使用每种激素相比,升压激素组合的功能反应增强。
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 .times. 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 .times. 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.