Tufro-McReddie A, Chevalier R L, Everett A D, Gomez R A
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville 22908.
Am J Physiol. 1993 Apr;264(4 Pt 2):R696-702. doi: 10.1152/ajpregu.1993.264.4.R696.
To determine whether decreased perfusion pressure affects the abundance and distribution of renin and its mRNA and the expression of the angiotensin II type 1 (AT1) receptor gene within the kidney, adult male Sprague-Dawley rats were subjected to aortic coarctation proximal to the renal arteries (Coarc, n = 8) and compared with sham-operated rats (Sham, n = 6). Renal renin distribution was determined by immunocytochemistry using a specific polyclonal antibody against rat renin. Renin mRNA was assessed by in situ hybridization to a 35S-labeled oligonucleotide complementary to rat renin mRNA. Kidney AT1 mRNA levels were determined by Northern analysis using a 1,133-base pair rat AT1 cDNA. Femoral arterial blood pressure, measured 24 h after surgery, was lower in Coarc than in Sham rats (75 +/- 5.4 vs. 122 +/- 2.3 mmHg, P < 0.05). Aortic coarctation increased the percent of juxtaglomerular apparatuses (%JGA) containing renin and its mRNA (85 +/- 2.5 and 66 +/- 2.8 vs. 49 +/- 5.3 and 36 +/- 1.7%, Coarc vs. Sham, P < 0.05) and the intensity of hybridization signals (497 +/- 89 vs. 71 +/- 12 grains/JGA, Coarc vs. Sham, P < 0.05). In addition, recruitment of renin gene expressing cells was observed along afferent arterioles in Coarc rats, whereas renin and its mRNA were limited to the JGAs in Sham rats. Renal AT1 receptor gene expression was threefold lower in Coarc than in Sham rats. We conclude that reduction of perfusion pressure after abdominal aortic coarctation acutely enhances renin gene expression and downregulates AT1 receptor gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
为了确定灌注压降低是否会影响肾脏中肾素及其mRNA的丰度和分布以及血管紧张素II 1型(AT1)受体基因的表达,对成年雄性Sprague-Dawley大鼠进行肾动脉近端主动脉缩窄(Coarc,n = 8),并与假手术大鼠(Sham,n = 6)进行比较。使用针对大鼠肾素的特异性多克隆抗体通过免疫细胞化学法测定肾脏肾素分布。通过与35S标记的与大鼠肾素mRNA互补的寡核苷酸进行原位杂交来评估肾素mRNA。使用1133个碱基对的大鼠AT1 cDNA通过Northern分析测定肾脏AT1 mRNA水平。术后24小时测量的股动脉血压,Coarc组低于Sham组大鼠(75±5.4对122±2.3 mmHg,P<0.05)。主动脉缩窄增加了含有肾素及其mRNA的肾小球旁器的百分比(%JGA)(85±2.5和66±2.8对49±5.3和36±1.7%,Coarc组对Sham组,P<0.05)以及杂交信号强度(497±89对71±12颗粒/JGA,Coarc组对Sham组,P<0.05)。此外,在Coarc组大鼠的入球小动脉沿线观察到了肾素基因表达细胞的募集,而在Sham组大鼠中肾素及其mRNA仅限于肾小球旁器。Coarc组大鼠的肾脏AT1受体基因表达比Sham组低三倍。我们得出结论,腹主动脉缩窄后灌注压降低会急性增强肾素基因表达并下调AT1受体基因表达。(摘要截断于250字)