Angiotensin type 1 receptor mediates renal production and conversion of prostaglandins E2 to F2α in conscious diabetic rats. (December 2015)

• Record Type: Journal Article
• Authors: Abadir, Peter M; Siragy, Helmy M
• Is Part Of: Journal of the renin-angiotensin-aldosterone system. Volume 16:Number 4(2015:Dec.)
• Page Start: 774
• Page End: 779
• Publication Date: 2015-12
• Subjects: Angiotensin II -- prostaglandin F2α -- prostaglandin E2 -- diabetes mellitus -- valsartan; Renin-angiotensin system -- Periodicals; 616.132
• DOI: 10.1177/1470320315592566
• Languages: English
• ISSNs: 1470-3203

Abstract

Introduction: Previous studies demonstrated that stimulation of angiotensin subtype 1 receptor (AT1 R) led to increased renal generation of prostaglandins E2 (PGE2 ) and renal inflammation. In turn, PGE2 increases AT1 R activity. The conversion of PGE2 to the less active metabolite prostaglandin F2α (PGF2α ) via 9-ketoreductase interrupts this feedback loop. The effects of diabetes on the interface between AT1 R, PGE2 and PGF2α are not well established. We hypothesized that in diabetes, an aberrant AT1 R 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 PGF2α in control and AT1 R blocker, valsartan, treated diabetic rats ( N =8 each). We utilized the PGF2α to PGE2 ratio as indirect measure of PGE 9-ketoreductase activity. Results: Diabetes increased renal interstitial fluid levels of Ang II, PGE2 and PGF2α . PGF2α /PGE2 ratio increased by the third week, but declined by the sixth week of diabetes. Valsartan reduced PGE2 and PGF2α levels and increased Ang II and the conversion of PGE2 to PGF2α . Conclusion: Our results suggest that in diabetes, AT1 R increases PGE2 generation and reduces conversion of PGE2 to PGF2 α with the progression of diabetes.