Effects of histamine and the H2 receptor antagonist ranitidine on ischemia-induced acute renal failure: Involvement of IL-6 and vascular endothelial growth factor

Ádám Vannay, Andrea Fekete, Veronika Müller, Jürgen Strehlau, Ondrej Viklicky, Tibor Veres, György Reusz, Tivadar Tulassay, Attila J. Szabó

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Vascular endothelial growth factor (VEGF) exerts cytoprotective, antiapoptotic and proangiogenic effects; its synthesis is induced by hypoxia, several cytokines and histamine. The effects of histamine and the H2 receptor antagonist ranitidine on renal VEGF and IL-6 synthesis were investigated in a well-established rat model of renal ischemia/reperfusion injury. Methods: Following 7 days of pretreatment with histamine (H group; n = 12), ranitidine (R group; n = 10) or vehicle (controls; n = 13), the left vascular pedicle was clamped for 50 min in uninephrectomized male rats and survival assessed in the different treatment groups. Additionally, renal IL-6 mRNA expression, as well as VEGF mRNA and protein abundance were measured in the three treatment groups following pretreatment only, 2 and 16 h after 50 min of renal ischemia (n = 6/group/timepoint). Results: Ranitidine significantly increased, while histamine significantly decreased survival following renal ischemia. Renal IL-6 mRNA expression increased 2 h after reperfusion in all groups and decreased thereafter, with the lowest level observed in the R group. While VEGF mRNA did not change in controls, histamine increased, whereas ranitidine decreased its expression during the follow-up. Two hours after ischemia a twofold increase in renal VEGF protein abundance was observed in controls and the H group and significantly higher values were noted in the R group at this time point. A further increase in VEGF protein was only present in the H group 16 h after reperfusion. Conclusion: These results indicate an important role of histamine in kidney damage following renal ischemia. The beneficial effects of ranitidine were partly mediated by decreased IL-6 and VEGF mRNA expression and significant early increase in renal VEGF abundance.

Original languageEnglish
Pages (from-to)105-113
Number of pages9
JournalKidney and Blood Pressure Research
Volume27
Issue number2
DOIs
Publication statusPublished - May 20 2004

Keywords

  • Histamine
  • IL-6
  • Ischemia
  • Kidney
  • Ranitidine
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Nephrology
  • Cardiology and Cardiovascular Medicine

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