Angiotensin type 1 receptor mediates renal production and conversion of prostaglandins E2 to F2α in conscious diabetic rats

Peter M. Abadir, Helmy M. Siragy

Research output: Contribution to journalArticle

Abstract

Introduction: Previous studies demonstrated that stimulation of angiotensin subtype 1 receptor (AT1R) led to increased renal generation of prostaglandins E2 (PGE2) and renal inflammation. In turn, PGE2 increases AT1R activity. The conversion of PGE2 to the less active metabolite prostaglandin F (PGF) via 9-ketoreductase interrupts this feedback loop. The effects of diabetes on the interface between AT1R, PGE2 and PGF are not well established. We hypothesized that in diabetes, an aberrant AT1R activity enhances the biosynthesis of PGE2 and impairs the activity of PGE 9-ketoreductase, leading to accumulation of PGE2. Materials and methods: Using microdialysis technique, we monitored renal interstitial fluid levels of angiotensin II (Ang II), PGE2 and PGF in control and AT1R blocker, valsartan, treated diabetic rats (N=8 each). We utilized the PGF to PGE2 ratio as indirect measure of PGE 9-ketoreductase activity. Results: Diabetes increased renal interstitial fluid levels of Ang II, PGE2 and PGF. PGF/PGE2 ratio increased by the third week, but declined by the sixth week of diabetes. Valsartan reduced PGE2 and PGF levels and increased Ang II and the conversion of PGE2 to PGF. Conclusion: Our results suggest that in diabetes, AT1R increases PGE2 generation and reduces conversion of PGE2 to PGF2α with the progression of diabetes.

Original languageEnglish (US)
Pages (from-to)774-779
Number of pages6
JournalJRAAS - Journal of the Renin-Angiotensin-Aldosterone System
Volume16
Issue number4
DOIs
StatePublished - Dec 1 2015

Keywords

  • Angiotensin II
  • Diabetes mellitus
  • Prostaglandin E
  • Prostaglandin F
  • Valsartan

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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