Department of Physiology, Universidad de Alcala, Alcala de Henares, Spain.
Hypertension. 2010 Sep;56(3):484-9. doi: 10.1161/HYPERTENSIONAHA.110.152587. Epub 2010 Aug 2.
The aim of the present experiments was to evaluate the differences in arterial pressure between H-Ras lacking mice and control mice and to analyze the mechanisms involved in the genesis of the differences. H-Ras lacking mice and mouse embryonic fibroblasts from these animals were used. Blood pressure was measured using 3 different methods: direct intraarterial measurement in anesthetized animals, tail-cuff sphygmomanometer, and radiotelemetry. H-Ras lacking mice showed lower blood pressure than control animals. Moreover, the aorta protein content of endothelial nitric oxide synthase, soluble guanylyl cyclase, and cyclic guanosine monophosphate-dependent protein kinase was higher in H-Ras knockout mice than in control animals. The activity of these enzymes was increased, because urinary nitrite excretion, sodium nitroprusside-stimulated vascular cyclic guanosine monophosphate synthesis, and phosphorylated vasoactive-stimulated phosphoprotein in aortic tissue increased in these animals. Furthermore, mouse embryonic fibroblasts from H-Ras lacking mice showed higher cyclic guanosine monophosphate-dependent protein kinase promoter activity than control cells. These results strongly support the upregulation of the nitric oxide-cyclic guanosine monophosphate pathway in H-Ras-deficient mice. Moreover, they suggest that H-Ras pathway could be considered as a therapeutic target for hypertension treatment.
本实验旨在评估缺乏 H-Ras 的小鼠与对照小鼠之间的动脉血压差异，并分析差异产生的机制。实验使用了缺乏 H-Ras 的小鼠和这些动物的胚胎成纤维细胞。采用 3 种不同方法测量血压：麻醉动物的直接动脉内测量、尾套血压计和无线电遥测。缺乏 H-Ras 的小鼠的血压低于对照动物。此外，H-Ras 敲除小鼠的主动脉内皮型一氧化氮合酶、可溶性鸟苷酸环化酶和环鸟苷酸依赖性蛋白激酶的蛋白含量高于对照动物。这些酶的活性增加，因为这些动物的尿中亚硝酸盐排泄、硝普钠刺激的血管环鸟苷酸合成和主动脉组织中磷酸化血管活性刺激磷蛋白增加。此外，缺乏 H-Ras 的小鼠的胚胎成纤维细胞显示出比对照细胞更高的环鸟苷酸依赖性蛋白激酶启动子活性。这些结果强烈支持 H-Ras 缺陷小鼠中一氧化氮-环鸟苷酸途径的上调。此外，它们表明 H-Ras 途径可以被视为治疗高血压的治疗靶点。
