title: Characteristic time courses of cortical and medullary sodium signals measured by noninvasive (23) Na-MRI in rat kidney induced by furosemide.
abstract: BACKGROUND
  To characterize regional kidney sodium response by MRI following NKCC2 inhibition.
  
  
  METHODS
  Regional renal sodium signals were monitored noninvasively using (23) Na-MRI at 9.4T with a temporal resolution of 1.5 min in anesthetized rats (N = 14). A mild NKCC2 inhibition was induced using a slow intravenous furosemide infusion. Time course of sodium signal was modeled as an exponential transient with a single characteristic time constant.
  
  
  RESULTS
  Under normal physiological conditions, the renal sodium signals in medullary and cortical regions were stable and found to respond differently to furosemide challenge. Furosemide infusion at 1.2 mg/kg/h (N = 7) increased sodium signal in the cortex by 40 ± 6% (P < 7 × 10(-5) ) whereas decreased in the medulla by 29 ± 2% (P < 3 × 10(-6) ) with different temporal kinetics. The characteristic time constants of the change were determined to be: 8 ± 2 and 70 ± 10 min for medulla and cortex. Also, the medullary change occurred 9(±3) times faster than cortical independent of furosemide infusion rate up to 35 mg/kg/h.
  
  
  CONCLUSIONS
  The pharmacological effects in terms of regional kidney sodium signal changes induced by NKCC2 inhibition are region-specific and highly predictable. Using noninvasive sodium MRI, we obtained regional renal sodium kinetics data sets in response to a low dose furosemide infusion in normal rats.
authors.affiliation: Imaging, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Haiying
authors.initials: H
authors.lastname: Liu
authors.affiliation: In vivo Pharmacology, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Ion Channel Department, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.affiliation: Ion Channel Department, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Kohler
authors.affiliation: Lab Animal Resources, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Shen
authors.affiliation: Imaging, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Donald S
authors.initials: DS
authors.lastname: Williams
authors.affiliation: Imaging, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Klimas
authors.affiliation: Neuroscience, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hargreaves
authors.affiliation: Ion Channel Department, Merck Research Labs, Kenilworth, New Jersey, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kaczorowski
mesh_terms: D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects*; D007679:Kidney Medulla / Q000187:drug effects*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*
chemical_list: D004232:Diuretics; D005665:Furosemide; D012964:Sodium
keywords: diuretics; kidney; regional kidney sodium; sodium MRI