Johns D W, Peach M J, Gomez R A, Inagami T, Carey R M
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Am J Physiol. 1990 Dec;259(6 Pt 2):F882-7. doi: 10.1152/ajprenal.1990.259.6.F882.
We investigated the effect of angiotensin II (ANG II) and enalapril on accumulation of renin messenger RNA (mRNA) and on renal renin distribution (immunohistochemical analysis). Adult Wistar-Kyoto rats received enalapril (0.2 mg/ml) in distilled drinking water for 8 or 12 days. On day 5 of enalapril treatment, an osmotic minipump was implanted in the peritoneum that caused sustained release of ANG II (200 ng.kg-1.min-1) or vehicle (bovine serum albumin) for 3 or 7 days. Control rats received water for 8 or 12 days and osmotic minipump implantation (containing vehicle solution) on the 5th day. Renin mRNA was identified by hybridization with a 32P-labeled full-length complementary DNA and was detected by autoradiography. Enalapril treatment increased renal renin mRNA specific activity (renin mRNA/total RNA). Subsequent infusion of angiotensin II for 3 or 7 days decreased renal renin mRNA specific activity. In addition, renin immunostaining increased along the afferent arteriole after enalapril treatment; however, enalapril-induced spread of renin immunostaining was not inhibited by ANG II. Thus ANG II attenuates the accumulation of renin mRNA stimulated by enalapril treatment without alteration of renal renin distribution. The lack of effect of ANG II on renal renin distribution may be due to the length of turnover time for stored protein. These findings suggest the shortloop negative feedback of ANG II on renin reflects inhibition of renin synthesis by ANG II. Therefore, we propose that ANG II exerts a direct inhibitory effect on renin by regulation of renin gene expression in renal vasculature.
我们研究了血管紧张素II（ANG II）和依那普利对肾素信使核糖核酸（mRNA）积累及肾脏肾素分布的影响（免疫组织化学分析）。成年Wistar-Kyoto大鼠饮用含依那普利（0.2 mg/ml）的蒸馏水8或12天。在依那普利治疗的第5天，将渗透微型泵植入腹膜，使其持续释放ANG II（200 ng·kg-1·min-1）或赋形剂（牛血清白蛋白）3或7天。对照大鼠饮用蒸馏水8或12天，并在第5天植入渗透微型泵（含赋形剂溶液）。通过与32P标记的全长互补DNA杂交鉴定肾素mRNA，并通过放射自显影检测。依那普利治疗增加了肾脏肾素mRNA的比活性（肾素mRNA/总RNA）。随后输注ANG II 3或7天降低了肾脏肾素mRNA的比活性。此外，依那普利治疗后，肾素免疫染色沿入球小动脉增加；然而，ANG II并未抑制依那普利诱导的肾素免疫染色扩散。因此，ANG II减弱了依那普利治疗刺激的肾素mRNA积累，而不改变肾脏肾素分布。ANG II对肾脏肾素分布缺乏影响可能是由于储存蛋白周转时间的长短。这些发现表明，ANG II对肾素的短环负反馈反映了ANG II对肾素合成的抑制作用。因此，我们提出ANG II通过调节肾血管中肾素基因的表达对肾素发挥直接抑制作用。
