The Effects of Chronic Metabolic Acidosis on Intrarenal Renin-Angiotensin System Activation and Erythropoietin Synthesis

• Main Authors: Hwee-Yeong Ng, 黃惠勇
• Other Authors: Hung-Chun Chen
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/27491347548111402471

碩士 === 高雄醫學大學 === 醫學研究所 === 98 === Background: Chronic metabolic acidosis is a common metabolic disturbance and its clinical impact can be severe and extensive. The role of intrarenal renin-angiotensin system (RAS) during metabolic acidosis is uncertain and how acidosis affects renal erythropoietin (EPO) synthesis remains unclear. The present study aimed to investigate intrarenal RAS and EPO synthesis in rats with excessive acid loading. Methods: Male Sprague-Dawley rats were fed on water containing 0.14M NH4Cl to induce metabolic acidosis. At 1 and 8 week interval, daily urine was collected for biochemical analysis and the experimental animals were harvested for blood sampling and renal tissue isolation. Gene expression analysis of RAS components, including renin, rennin/prorenin receptor, angiotensinogen, converting enzyme (ACE), angiotesin II type 1 and 2 receptor (AT1R/AT2R) and EPO was assessed by RT-PCR. Protein abundance was confirmed by Western-blot test and serum EPO concentration was determined. Results: Lower blood pH and bicarbonate concentration were found in 1 week NH4Cl treated rats but not in 8 weeks treatment group. There was an increased daily proteinuria in acid loaded rats (2.49 ± 1.07 mg/100g vs. 6.78 ± 2.03 mg/100g of 1 week group; 5.68 ± 1.40 mg/100g of 8 weeks group, both p<0.05) as well as significant hypercalciuria and hyperphosphaturia. In 1 week acidotic rats, significant upregulation of angiotensinogen (359.6 ± 62.4% of control), ACE (577.8 ± 107.3%), AT1R (194.1 ± 25.2%) and AT2R (4629.4 ± 1525.5%) were found. EPO gene expression was also upregulated (4356.5 ± 1695.5%, all p<0.05) in 1 week acid loaded rats. But both serum EPO and hemoglobin levels were decreased. In 8 weeks group, a significant increased AT1R expression was observed. Conclusion: Metabolic acidosis induced proteinuria in association with activation of intrarenal RAS and upregulation of EPO gene expression. In contrast, metabolic acidosis caused anemia and reduced serum EPO concentration. Our study provided valuable information about the pathophysiological change during excessive acid loading.