Effects of AT1 and AT2 receptor blockade on angiotensin II induced apoptosis of human renal proximal tubular epithelial cells.
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.


CONCLUSIONS
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.
Weidekamm
Claudia
C
Division of Nephrology and Dialysis, Department of Internal Medicine III, University of Vienna.
Hauser
Peter
P
Hansmann
Cornelia
C
Schwarz
Christoph
C
Klingler
Hans
H
Mayer
Gert
G
Oberbauer
Rainer
R
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan