Department of Pathophysiology and Gerontology, Medical School, University of Pecs, Hungary
J Gerontol A Biol Sci Med Sci. 2014 May;69(5):519-26. doi: 10.1093/gerona/glt128. Epub 2013 Sep 7.
In this study, we hypothesized that aging alters angiotensin II (Ang II)-induced vasomotor responses and expression of vascular mRNA and protein angiotensin type 1 receptor (AT1R). Thus, carotid arteries were isolated from the following age groups of rats: 8 days, 2-9 months, 12-20 months, and 20-30 months, and their vasomotor responses were measured in a myograph after repeated administrations of Ang II. Vascular relative AT1R mRNA level was determined by quantitative reverse-transcriptase polymerase chain reaction and the AT1R protein density was measured by Western blot. Contractions to the first administration of Ang II increased from 8 days to 6 months and then they decreased to 30 months. In general, second administration of Ang II elicited reduced contractions, but they also increased from 8 days until 2 months and then they decreased to 30 months. Similarly the AT1R mRNA level increased from 8 days to 12 months and then decreased to 30 months. Similarly the AT1R protein density increased from 8 days until 16 months and then they decreased to 30 months. The pattern of these changes correlated with functional vasomotor data. We conclude that aging (newborn to senescence) has substantial effects on Ang II-induced vasomotor responses and AT1R signaling suggesting the importance of genetic programs.
在这项研究中,我们假设衰老改变了血管紧张素 II(Ang II)诱导的血管舒缩反应以及血管 mRNA 和蛋白血管紧张素 1 型受体(AT1R)的表达。因此,我们从以下年龄段的大鼠中分离出颈动脉:8 天、2-9 个月、12-20 个月和 20-30 个月,并在肌动描记器中重复给予 Ang II 后测量其血管舒缩反应。通过定量逆转录聚合酶链反应测定血管相对 AT1R mRNA 水平,并通过 Western blot 测定 AT1R 蛋白密度。第一次给予 Ang II 引起的收缩从 8 天增加到 6 个月,然后减少到 30 个月。一般来说,第二次给予 Ang II 引起的收缩减少,但它们也从 8 天增加到 2 个月,然后减少到 30 个月。同样,AT1R mRNA 水平从 8 天增加到 12 个月,然后减少到 30 个月。同样,AT1R 蛋白密度从 8 天增加到 16 个月,然后减少到 30 个月。这些变化的模式与功能血管舒缩数据相关。我们得出结论,衰老(从新生儿到衰老)对 Ang II 诱导的血管舒缩反应和 AT1R 信号有显著影响,这表明遗传程序的重要性。