Chou Hsiu-Chu, Wang Leng-Fang, Lu Kuo-Shyan, Chen Chung-Ming
Department of Anatomy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Acta Histochem. 2008;110(6):497-504. doi: 10.1016/j.acthis.2008.01.002. Epub 2008 Apr 1.
Intrauterine growth restriction (IUGR) can program the future development of hypertension in adulthood. The renin-angiotensin system has been reported to play a role in IUGR-induced hypertension. The aims of this study were to investigate the effects of IUGR on renal angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and chymase in IUGR-induced hypertension. Timed pregnant Sprague-Dawley rats received 50% rations of control food intakes from days 15 to 21 of gestation. Control rats received regular food throughout the pregnancies. Arterial blood pressure and glomerular number were measured and immunohistochemical studies were performed on kidney tissues in adult male offspring at 16 weeks of age. IUGR rats exhibited significantly lower body and kidney weights and reduced number of glomeruli when compared with control rats. IUGR rats had significantly higher systolic blood pressure than control rats. Immunoreactivity of ACE was comparable between control and IUGR rats whereas immunoreactivities of chymase and Ang II were significantly higher in IUGR rats than in control rats. In conclusion, immunohistochemical studies document up-regulation of ACE-independent Ang II and chymase in IUGR kidney and indicate that overactivity of chymase may result in increased intrarenal Ang II production, which could contribute to the development of hypertension in intrauterine undernourished rats.
宫内生长受限(IUGR)可影响成年后高血压的未来发展。据报道,肾素-血管紧张素系统在IUGR诱导的高血压中起作用。本研究的目的是探讨IUGR对IUGR诱导的高血压大鼠肾血管紧张素转换酶(ACE)、血管紧张素II(Ang II)和糜酶的影响。将定时受孕的Sprague-Dawley大鼠在妊娠第15至21天给予50%的对照食物摄入量。对照大鼠在整个孕期给予常规食物。在16周龄的成年雄性后代中测量动脉血压和肾小球数量,并对肾组织进行免疫组织化学研究。与对照大鼠相比,IUGR大鼠的体重和肾脏重量显著降低,肾小球数量减少。IUGR大鼠的收缩压显著高于对照大鼠。对照大鼠和IUGR大鼠之间ACE的免疫反应性相当,而IUGR大鼠中糜酶和Ang II的免疫反应性显著高于对照大鼠。总之,免疫组织化学研究表明IUGR肾脏中ACE非依赖性Ang II和糜酶上调,提示糜酶活性过高可能导致肾内Ang II生成增加,这可能有助于宫内营养不良大鼠高血压的发生。