el-Dahr S S, Gee J, Dipp S, Hanss B G, Vari R C, Chao J
Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Am J Physiol. 1993 May;264(5 Pt 2):F874-81. doi: 10.1152/ajprenal.1993.264.5.F874.
The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood pressure (SBP) and plasma angiotensin (ANG) II levels were significantly higher at 1 and 5 wk of obstruction than in sham-operated groups. Also, plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05), and plasma angiotensin-converting enzyme (ACE)-kininase II activity was elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan (Dup 753) prevented the rise in SBP after UUO and normalized SBP in chronically hypertensive UUO rats. Renin mRNA levels and ANG II content were elevated in the obstructed kidneys at 1 and 5 wk compared with sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated in both the obstructed and contralateral kidneys at 5 wk compared with sham-operated kidneys (P < 0.05). In marked contrast to renin, total immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1 and 5 wk (P < 0.001). The results indicate that urinary obstruction activates renin and suppresses kallikrein gene expression. Activation of ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation and kinin degradation. The results implicate ANG II overproduction and kinin deficiency in the pathogenesis of UUO-induced hypertension and intrarenal vasoconstriction.
本研究的目的是阐明大鼠单侧输尿管梗阻（UUO）持续较长时间（1周和5周）对肾内肾素 - 血管紧张素系统和激肽释放酶 - 激肽系统的影响。梗阻1周和5周时的收缩压（SBP）和血浆血管紧张素（ANG）II水平显著高于假手术组。此外，血浆肾素活性和ANG I水平在1周时升高（P < 0.05），血浆血管紧张素转换酶（ACE） - 激肽酶II活性在5周时升高（P < 0.05）。用氯沙坦（Dup 753）阻断ANG II受体可防止UUO后SBP升高，并使慢性高血压UUO大鼠的SBP恢复正常。与假手术肾脏相比，梗阻肾脏在1周和5周时肾素mRNA水平和ANG II含量升高（P < 0.05）。与假手术肾脏相比，梗阻肾脏和对侧肾脏在5周时ACE - 激肽酶II活性均升高（P < 0.05）。与肾素形成鲜明对比的是，梗阻肾脏中总的免疫反应性激肽释放酶含量和组织激肽释放酶mRNA水平在1周和5周时均降至假手术肾脏的25%（P < 0.001）。结果表明尿路梗阻激活肾素并抑制激肽释放酶基因表达。UUO对ACE - 激肽酶II的激活也有助于增强肾内ANG II的生成和激肽降解。结果提示ANG II过度产生和激肽缺乏在UUO诱导的高血压和肾内血管收缩的发病机制中起作用。
