title: Angiotensin type 1 receptor mediates renal production and conversion of prostaglandins E2 to F2α in conscious diabetic rats.
abstract: BACKGROUND
  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 F2α (PGF2α) via 9-ketoreductase interrupts this feedback loop. The effects of diabetes on the interface between AT1R, PGE2 and PGF2α 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.
  
  
  METHODS
  Using microdialysis technique, we monitored renal interstitial fluid levels of angiotensin II (Ang II), PGE2 and PGF2α in control and AT1R 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.
  
  
  CONCLUSIONS
  Our results suggest that in diabetes, AT1R increases PGE2 generation and reduces conversion of PGE2 to PGF2α with the progression of diabetes.
authors.affiliation: Johns Hopkins University, Division of Geriatrics Medicine and Gerontology, Baltimore, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Abadir
authors.affiliation: University of Virginia School of Medicine, Department of Medicine, Charlottesville, USA hms7a@virginia.edu.
authors.forename: Helmy M
authors.initials: HM
authors.lastname: Siragy
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D003243:Consciousness; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015237:Dinoprost / Q000096:biosynthesis*; D015232:Dinoprostone / Q000096:biosynthesis*; D045604:Extracellular Fluid / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D015237:Dinoprost; D015232:Dinoprostone
keywords: Angiotensin II; diabetes mellitus; prostaglandin E2; prostaglandin F2α; valsartan