Phospholipase C responses in cells from spontaneously hypertensive rats.
Phospholipase C responses in cells from spontaneously hypertensive rats.
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自发性高血压大鼠细胞中磷脂酶 C 的反应。
DOI：
10.1161/01.hyp.19.5.446
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Dunn,MJ
中科院分区：
文献类型：
--
作者：
Osanai,T;Dunn,MJ
我们检验了这样的假设：自发性高血压大鼠全身血管阻力增加可能是继发于血管收缩刺激引起的磷脂酶C活性增强。在培养的肾小球系膜细胞和肠系膜血管平滑肌细胞中比较了血管紧张素II（Ang II）、血栓素A2、精氨酸加压素和内皮素-1对磷脂酶C的激活作用，这些细胞取自13- 14周龄的高血压和血压正常的Wistar-Kyoto大鼠（血压，185 +/- 1与135 +/- 2 mm Hg）。磷脂酶C通过测量胞质游离钙和放射性标记的肌醇磷酸的积累进行评估。取自两种品系的系膜细胞之间的基础胞浆钙没有差异，但高血压大鼠的平滑肌细胞中的基础胞浆钙较高（210.1 +/- 8.2与149.2 +/- 4.7 nM）。在高血压大鼠的系膜细胞中，细胞质钙和磷酸肌醇积累对Ang II的反应性显着增强（10（-7）M Ang II：钙峰值增加，1，266 +/- 181 vs 603 +/- 93 nM; 1分钟时磷酸肌醇的百分比增加，266 +/- 26 vs 98 +/- 10%）。高血压大鼠的血管平滑肌细胞，与血压正常大鼠相比，血管紧张素II刺激的细胞内钙和磷酸肌醇显示出类似的增强。血栓素A2诱导的血管平滑肌细胞内钙和磷酸肌醇积累的增强在高血压动物中也更大。然而，在正常血压和高血压动物之间，肾小球系膜或血管平滑肌细胞对血管加压素和内皮素的反应没有差异。高血压和正常血压来源的系膜细胞之间的血管紧张素II受体的数量和亲和力没有显着差异。我们的结论是，在大鼠中的遗传性血压升高可能是次要的增强后受体信号在肾小球系膜细胞激活的血管紧张素II和血管平滑肌细胞刺激血管紧张素II或血栓素A2增强信号。
We tested the hypothesis that increased systemic vascular resistance in spontaneously hypertensive rats may be secondary to enhanced phospholipase C activity in response to vasoconstrictor stimuli. Activation of phospholipase C by angiotensin II (Ang II), thromboxane A2, arginine vasopressin, and endothelin-1 was compared in cultured glomerular mesangial cells and mesenteric vascular smooth muscle cells taken from 13- to 14-week-old hypertensive and normotensive Wistar-Kyoto rats (blood pressure, 185 +/- 1 versus 135 +/- 2 mm Hg). Phospholipase C was assessed by measuring cytosolic free calcium and by the accumulation of radiolabeled inositol phosphates. Basal cytosolic calcium did not differ between mesangial cells taken from both strains but was greater in smooth muscle cells from hypertensive rats (210.1 +/- 8.2 versus 149.2 +/- 4.7 nM). The responsiveness of cytosolic calcium and inositol phosphate accumulation to Ang II was significantly enhanced in mesangial cells from hypertensive rats (10(-7) M Ang II: peak increase of calcium, 1,266 +/- 181 versus 603 +/- 93 nM; percent increment of inositol phosphates at 1 minute, 266 +/- 26 versus 98 +/- 10%). Vascular smooth muscle cells from hypertensive rats, when compared with normotensive rats, showed a similar augmentation of Ang II-stimulated intracellular calcium and inositol phosphates. Thromboxane A2-induced enhancement of intracellular calcium and inositol phosphate accumulation in vascular smooth muscle cells was also greater in hypertensive animals. However, the responses to vasopressin and endothelin in mesangial or vascular smooth muscle cells did not differ between the normotensive and hypertensive animals. There was no significant difference in Ang II receptor number and affinity between hypertensive- and normotensive-derived mesangial cells. We conclude that genetically increased blood pressure in rats may be secondary to enhanced post-receptor signaling in glomerular mesangial cells activated by Ang II and to enhanced signaling in vascular smooth muscle cells stimulated by either Ang II or thromboxane A2.