Nishimura M, Milsted A, Block C H, Brosnihan K B, Ferrario C M
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195.
Hypertension. 1992 Aug;20(2):158-67. doi: 10.1161/01.hyp.20.2.158.
Angiotensinogen messenger RNA (mRNA) levels were measured in the brain (hypothalamus, lower brain stem, cerebellum), liver, kidneys, and adrenal glands of rats made hypertensive by ligation of the aorta between the renal arteries. We also measured renin mRNA in the kidneys of these renal hypertensive rats. The early phase of hypertension (day 6) was associated with significant increases in plasma renin activity and levels of circulating angiotensin II. The circulating renin-angiotensin system was not activated in the later phase of hypertension (day 24). Angiotensinogen mRNA levels were elevated in the lower brain stem of hypertensive rats at both stages of hypertension. In contrast, angiotensinogen mRNA levels in the hypothalamus were increased only at day 6 after aortic ligation. Decreased levels of angiotensinogen mRNA were observed in the cerebellum in both the early and later phases of the hypertension. Angiotensinogen mRNA levels in the adrenal gland below the ligature fell in the early phases but rose in the later phases of hypertension. Renin mRNA levels of the ischemic kidney remained elevated at both the early and later phases, whereas in both ischemic and nonischemic kidneys, levels of angiotensinogen mRNA remained below sham values throughout the period of study. These results indicate differential expression of renin-angiotensin system mRNAs in tissues of renal hypertensive rats. The differential changes in the expression of angiotensinogen mRNA over the course of development and maintenance of renal hypertension suggest that factors in addition to angiotensin II are important in modulating the expression of renin-angiotensin system genes.
通过结扎肾动脉之间的主动脉使大鼠患高血压,然后测量其大脑(下丘脑、脑桥下部、小脑)、肝脏、肾脏和肾上腺中的血管紧张素原信使核糖核酸(mRNA)水平。我们还测量了这些肾性高血压大鼠肾脏中的肾素mRNA。高血压早期(第6天)与血浆肾素活性和循环血管紧张素II水平的显著升高有关。在高血压后期(第24天),循环肾素-血管紧张素系统未被激活。在高血压的两个阶段,高血压大鼠脑桥下部的血管紧张素原mRNA水平均升高。相比之下,仅在主动脉结扎后第6天,下丘脑的血管紧张素原mRNA水平升高。在高血压的早期和后期,小脑中血管紧张素原mRNA水平均降低。结扎下方肾上腺中的血管紧张素原mRNA水平在高血压早期下降,但在后期升高。缺血肾脏的肾素mRNA水平在早期和后期均保持升高,而在整个研究期间,缺血和非缺血肾脏中的血管紧张素原mRNA水平均低于假手术组的值。这些结果表明肾性高血压大鼠组织中肾素-血管紧张素系统mRNA的差异表达。在肾性高血压的发展和维持过程中,血管紧张素原mRNA表达的差异变化表明,除血管紧张素II外,其他因素在调节肾素-血管紧张素系统基因的表达中也很重要。