Vascular smooth muscle cells from the Milan hypertensive rat exhibit decreased functional angiotensin II receptors.
Vascular smooth muscle cells from the Milan hypertensive rat exhibit decreased functional angiotensin II receptors.
复制标题
米兰高血压大鼠的血管平滑肌细胞表现出功能性血管紧张素 II 受体减少。
DOI：
10.1161/01.hyp.15.6.591
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Canessa,M
中科院分区：
文献类型：
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作者：
Socorro,L;Vallega,G;Nunn,A;Moore,TJ;Canessa,M
本研究旨在研究低肾素高血压模型米兰高血压大鼠(MHS)血管紧张素II(Ang II)结合部位的功能特性。通过群体倍增时间(24.5+/-2和34.8+/-2小时，n=4)，MHS大鼠的平滑肌细胞在培养中表现出比米兰正常血压株(MNS)更多的生长。通过使用[125I]Ang II的结合试验评估激素受体数量，表明两种细胞的受体数量或亲和力都没有差异。通过测定磷脂酶C的活性、Na(+)-H+交换和胞内钙离子水平来评价Ang II受体的功能反应性。在10(-7)M Ang II作用15秒前后，用氚标记的三磷酸肌醇和双磷酸盐释放磷脂酶C来测定磷脂酶C的活性。Ang II刺激MNS的磷脂酶C活性(p<0.02)，但不刺激MHS细胞。在MNS细胞中，Ang II显著刺激(p<0.001)逆向转运体活性，而在MHS细胞中，Ang II无明显刺激作用，表现为一致钝化的反应。MHS细胞胞浆基础钙水平高于MNS细胞，但在Ang II存在下，MNS细胞内钙离子水平迅速升高，而MHS细胞内钙离子水平无明显变化。在通透性细胞中，GTP-γ-S对磷脂酶C的直接激活表明，两株菌通过鸟嘌呤-核苷酸结合蛋白表现出相似的偶联水平。
The present study was designed to study the functional properties of Angiotensin II (Ang II) binding sites in vascular smooth muscle cells in the Milan hypertensive rat (MHS), a model of low renin hypertension. Smooth muscle cells from MHS rats exhibited increased growth in culture in comparison with the Milan normotensive strain (MNS) as determined by population doubling times (24.5 +/- 2 and 34.8 +/- 2 hours, n = 4, respectively). Hormone receptor number, evaluated by binding assays using [125I]Ang II, showed no difference in either receptor number or affinity for both cell types. The functional responsiveness of Ang II receptors was evaluated by measuring the activation of phospholipase C, Na(+)-H+ exchange, and cytosolic Ca2+ levels. Phospholipase C activity was determined as tritium-labeled inositol trisphosphate and bisphosphate release before and after 15-second exposure to 10(-7) M Ang II. Ang II-stimulated phospholipase C activity in MNS (p less than 0.02) but not in MHS cells. Na(+)-H+ exchange was measured as the dimethylamiloride-sensitive 22Na+ influx into acid-loaded vascular smooth muscle cells with and without 10(-7) M Ang II. In MNS cells, Ang II significantly stimulated (p less than 0.001) antiporter activity but not in MHS cells, which showed a uniformly blunted response. MHS cells exhibited higher basal cytosolic Ca2+ levels than MNS cells, but Ca2+ rapidly increased in the presence of Ang II in MNS but not in MHS cells. Direct activation of phospholipase C by GTP-gamma-S in permeabilized cells indicated that both strains exhibited similar coupling levels by guanine-nucleotide binding proteins.(ABSTRACT TRUNCATED AT 250 WORDS)