BACKGROUND: Tubular atrophy is a common histological feature of chronic renal failure, and epithelial cell death by apoptosis might play an important role in its pathogenesis. Angiotensin II contributes to the progressive nature of many kidney diseases and treatment with angiotensin converting enzyme inhibitors preserves the structure of the tubulointerstitial compartment in human and experimental renal diseases. METHODS: Primary cultures of human renal proximal tubular epithelial cells were co-incubated with angiotensin II alone or in combination with the angiotensin II AT1 receptor antagonist losartan or/and the AT2 antagonist PD123319. Apoptosis was determined after 20 hours by TUNEL staining and flow cytometry. RESULTS: Angiotensin II at concentrations of 10(-9) M induced apoptosis (control vs. angiotensin II 4 +/- 3% vs. 73 +/- 11%; p < 0.05). This effect was completely offset by co-incubation with the angiotensin II AT2 receptor blocker at concentrations 10(-7) M (control vs. PD123319 4 +/- 3% vs. 8 +/- 3%; p < 0.05); AT1 blockade was ineffective in apoptosis inhibition. When both angiotensin receptors were blocked, no additional effect on apoptosis inhibition could be detected. CONCLUSION: We provided evidence, that physiological concentrations of angiotensin II can induce apoptosis of human renal proximal tubule epithelial cells. This effect is mediated via AT2 receptors.
BACKGROUND:Tubular atrophy is a common histological feature of chronic renal failure, and epithelial cell death by apoptosis might play an important role in its pathogenesis. Angiotensin II contributes to the progressive nature of many kidney diseases and treatment with angiotensin converting enzyme inhibitors preserves the structure of the tubulointerstitial compartment in human and experimental renal diseases. METHODS: Primary cultures of human renal proximal tubular epithelial cells were co-incubated with angiotensin II alone or in combination with the angiotensin IIAT1 receptor antagonist losartan or/and the AT2 antagonist PD123319. Apoptosis was determined after 20 hours by TUNEL staining and flow cytometry. RESULTS:Angiotensin II at concentrations of 10(-9) M induced apoptosis (control vs. angiotensin II 4 +/- 3% vs. 73 +/- 11%; p < 0.05). This effect was completely offset by co-incubation with the angiotensin IIAT2 receptor blocker at concentrations 10(-7) M (control vs. PD123319 4 +/- 3% vs. 8 +/- 3%; p < 0.05); AT1 blockade was ineffective in apoptosis inhibition. When both angiotensin receptors were blocked, no additional effect on apoptosis inhibition could be detected. CONCLUSION: We provided evidence, that physiological concentrations of angiotensin II can induce apoptosis of human renal proximal tubule epithelial cells. This effect is mediated via AT2 receptors.
Authors: Sadashiva S Karnik; Hamiyet Unal; Jacqueline R Kemp; Kalyan C Tirupula; Satoru Eguchi; Patrick M L Vanderheyden; Walter G Thomas Journal: Pharmacol Rev Date: 2015-10 Impact factor: 25.468
Authors: Ana Konvalinka; Joyce Zhou; Apostolos Dimitromanolakis; Andrei P Drabovich; Fei Fang; Susan Gurley; Thomas Coffman; Rohan John; Shao-Ling Zhang; Eleftherios P Diamandis; James W Scholey Journal: J Biol Chem Date: 2013-07-11 Impact factor: 5.157