title: Effects of chronic rosiglitazone treatment on renal handling of salt and water in rats with volume-overload congestive heart failure.
abstract: BACKGROUND
  The side effects of fluid retention and edema of the thiazolidinedione (TZD) class of peroxisome proliferator-activated receptor-γ agonists limit their use in patients with congestive heart failure (CHF). The present study aims to explore whether chronic treatment with the TZD compound rosiglitazone (RGZ) is associated with worsening of salt and water retention in male Sprague-Dawley rats with aorto-caval fistula, an experimental model of volume-overload CHF.
  
  
  RESULTS
  The effects of oral RGZ (30 mg/kg per day for 4 weeks) in CHF rats on plasma volume, cumulative sodium excretion, renal expression of Na(+) channels and transporters, and selected biomarkers of CHF were compared with those in CHF rats and sham-operated control rats treated with vehicle only (n=7 to 10). Additionally, the response to acute saline loading (3.5% of body weight) was evaluated after 2 weeks of treatment by renal clearance methodology. Chronic RGZ treatment caused no further increase in plasma volume compared with vehicle-treated CHF rats. Moreover, no increase in renal expression of Na(+) transport-linked channels/transporters was observed in response to RGZ. Cumulative sodium excretion was enhanced in CHF rats after RGZ and by another TZD compound, pioglitazone. In response to saline loading, RGZ-treated animals displayed a higher natriuretic/diuretic response than did vehicle-treated rats. Chronic RGZ treatment was not associated with any deterioration in selected biomarkers of CHF, whereas indices of cardiac hypertrophy and blood pressure were improved.
  
  
  CONCLUSIONS
  Chronic RGZ treatment was not associated with worsening of fluid retention or cardiac status in rats with experimental volume-overload CHF. Rather, RGZ appeared to improve renal handling of salt and water in rats with CHF.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Technion-IIT, Haifa, Israel.
authors.forename: Ilia
authors.initials: I
authors.lastname: Goltsman
authors.forename: Xinkang
authors.initials: X
authors.lastname: Wang
authors.forename: Edward R
authors.initials: ER
authors.lastname: Lavallie
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Diblasio-Smith
authors.forename: Elena
authors.initials: E
authors.lastname: Ovcharenko
authors.forename: Aaron
authors.initials: A
authors.lastname: Hoffman
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
authors.forename: Giora Z
authors.initials: GZ
authors.lastname: Feuerstein
authors.forename: Joseph
authors.initials: J
authors.lastname: Winaver
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D012965:Sodium Chloride / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects*; D014883:Water-Electrolyte Imbalance / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D045162:Thiazolidinediones; D014867:Water; D000077154:Rosiglitazone; D012965:Sodium Chloride