Angiotensin II receptor blocker inhibits tumour necrosis factor-alpha-induced cell damage in human renal proximal tubular epithelial cells

Aim: We investigated the effect of angiotensin II (AII) type 1 (AT1) and angiotensin II type 2 (AT2) receptor blockers on tumour necrosis factor alpha (TNF‐α)‐induced cell damage in human renal proximal tubular epithelial cells (RPTEC). Methods: The lactate dehydrogenase (LDH) and N‐acetyl‐beta‐glucosaminidase (NAG) release into the medium after TNF‐α treatment in RPTEC were determined using modified commercial procedures. In addition, the levels of caspase 3/7 activity in RPTEC were measured after TNF‐α treatment with ΑΤ1 or AT2 receptor blockers. Finally we investigated the change of p22phox protein levels after TNF‐α with ΑΤ1 or AT2 receptor blockers in RPTEC. Results: Tumour necrosis factor alpha (10^?8 mol/L) significantly increased LDH and NAG release into the medium from RPTEC. ΑΤ1 receptor blockers, olmesartan and valsartan (10^?9?10^?6 mol/L) showed a significant reduction on TNF‐α‐induced LDH and NAG release in RPTEC. AT2 receptor blocker, PD123319 (10^?7?10^?5 mol/L) also decreased TNF‐α‐induced LDH and NAG release in RPTEC. Blockade of both ΑΤ1 and AT2 receptor indicated additional reduction on TNF‐α‐induced LDH and NAG release. TNF‐α (10^?8 mol/L) treatment showed small but significant increases of caspase 3/7 activity in RPTEC, and AT1 and AT2 receptor blockers (10^?8 mol/L) comparably decreased TNF‐α‐induced caspase 3/7 activity. Significant increases of p22phox protein levels were observed in TNF‐α‐treated group in RPTEC. However, only ΑΤ1 (10^?8 mol/L) but not AT2 (10^?5 mol/L) receptor blocker significantly decreased TNF‐α‐induced p22phox protein levels. Conclusion: The present study demonstrates that TNF‐α induces renal tubular cell damage in RPTEC and AT1/AT2 receptor blockers showed cytoprotective effects probably via at least partly different mechanism.