title: Decreased renal AT1 receptor binding in rats after subtotal nephrectomy: PET study with [(18)F]FPyKYNE-losartan.
abstract: BACKGROUND
  Significant renal mass reduction induced by 5/6 subtotal nephrectomy (Nx) is associated with a chain of events that culminates in hypertension and chronic kidney disease (CKD). Numerous studies have provided evidence for the role of angiotensin (Ang) II type 1 receptor (AT1R) in the promotion and progression of the disease; however, conflicting results were reported on intrarenal AT1R levels in CKD models.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 26) underwent Nx or sham operations. Animals were scanned at 8-10 weeks post-surgery with PET using the novel AT1R radioligand [(18)F]FPyKYNE-losartan. Radioligand binding was quantified by kidney-to-blood ratio (KBR), standard uptake value (SUV), and distribution volume (DV). After sacrifice, plasma and kidney Ang II levels were measured. Western blot and (125)I-[Sar(1), Ile(8)]Ang II autoradiography were performed to assess AT1R expression.
  
  
  RESULTS
  At 8-10 weeks post-surgery, Nx rats developed hypertension, elevated plasma creatinine levels, left ventricle hypertrophy, increased myocardial blood flow (MBF), and reduced Ang II levels compared to shams. PET measurements displayed significant decrease in KBR (29 %), SUV (24 %), and DV (22 %) induced by Nx (p < 0.05), and these findings were confirmed by in vitro assays.
  
  
  CONCLUSIONS
  Reduced renal AT1Rs in hypertensive rats measured with [(18)F]FPyKYNE-losartan PET at 8-10 weeks following Nx support further use of this non-invasive approach in longitudinal studies to better understand the AT1R role in CKD progression.
authors.affiliation: National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
authors.forename: Basma
authors.initials: B
authors.lastname: Ismail
authors.affiliation: National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: deKemp
authors.affiliation: National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada.
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Hadizad
authors.affiliation: National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Mackasey
authors.affiliation: National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada.|Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
authors.forename: Rob S
authors.initials: RS
authors.lastname: Beanlands
authors.affiliation: National Cardiac PET Centre, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, ON, K1Y 4W7, Canada. jean.dasilva@umontreal.ca.|Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. jean.dasilva@umontreal.ca.|Department of Radiology, Radio-Oncology and Nuclear Medicine, University of Montreal, University of Montreal Hospital Research Centre (CRCHUM), 900 Rue Saint-Denis, Montréal, Québec, H2X 0A9, Canada. jean.dasilva@umontreal.ca.
authors.forename: Jean N
authors.initials: JN
authors.lastname: DaSilva
keywords: 18F-losartan; Angiotensin II; Chronic kidney disease; Hypertension; PET imaging