Sinnayah P, Kachab E, Haralambidis J, Coghlan J P, McKinley M J
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Brain Res Mol Brain Res. 1997 Oct 15;50(1-2):43-50. doi: 10.1016/s0169-328x(97)00165-4.
The role of centrally synthesised angiotensinogen in neural mechanisms subserving water drinking in rats was investigated by injecting antisense oligonucleotides complementary to rat angiotensinogen mRNA into the brain with the aim of inhibiting cerebral angiotensinogen synthesis. Phosphorothioate antisense oligonucleotides (18 mer) encompassing the translation start codon were injected into the lateral ventricle of rats and their responses to a number of dipsogenic stimuli tested. These were: intracerebroventricular (i.c.v.) renin, i.c.v. angiotensin II, i.c.v. carbachol, subcutaneous isoproterenol, intravenous hypertonic saline, water deprivation for 24 h or subcutaneous injection of polyethylene glycol. Antisense treatment significantly reduced (by approximately 50%) the volume of water drunk in response to i.c.v. injection of renin or subcutaneous isoproterenol, but did not reduce water intake elicited by the other dipsogenic stimuli. The i.c.v. administration of mismatch, scrambled or sense oligonucleotides did not inhibit water intake. These data suggest that centrally produced angiotensinogen may have a role in neural pathways subserving isoproterenol-induced drinking.
通过向大鼠脑内注射与大鼠血管紧张素原mRNA互补的反义寡核苷酸以抑制脑内血管紧张素原的合成，研究了中枢合成的血管紧张素原在大鼠饮水的神经机制中的作用。将包含翻译起始密码子的硫代磷酸反义寡核苷酸（18聚体）注入大鼠侧脑室，并测试它们对多种致渴刺激的反应。这些刺激包括：脑室内（i.c.v.）注射肾素、脑室内注射血管紧张素II、脑室内注射卡巴胆碱、皮下注射异丙肾上腺素、静脉注射高渗盐水、禁水24小时或皮下注射聚乙二醇。反义治疗显著降低了（约50%）对脑室内注射肾素或皮下注射异丙肾上腺素的饮水体积，但并未减少其他致渴刺激引起的水摄入量。脑室内给予错配、乱序或正义寡核苷酸并未抑制水摄入。这些数据表明，中枢产生的血管紧张素原可能在介导异丙肾上腺素诱导饮水的神经通路中发挥作用。
