title: Investigation of aldosterone-synthase inhibition in rats.
abstract: BACKGROUND
  In-vivo investigation of aldosterone-synthase inhibitors requires experimental models to characterize the biological effects of these compounds.
  
  
  METHODS
  Seven successive experiments were performed in groups of 2-month-old male spontaneously hypertensive rats. Urinary free aldosterone was the main end-point measured during two contrasted diets: low sodium-high potassium (LS), inducing high urinary aldosterone (839 pmol/24 h, 95% confidence interval 654-1077), and high sodium-normal potassium (HS), inducing low urinary aldosterone (38.1 pmol/24 h; 95% confidence interval, 32.4-44.9).
  
  
  RESULTS
  FAD 286 A (10 and 30 mg/kg) decreased urinary free aldosterone by 53 and 87% on the LS diet, and 50 and 75% on the HS. Plasma renin concentration increased three-fold after a 4-week treatment of 30 mg/kg FAD 286 A on the LS diet and did not change on the HS. The combination of FAD 286 A (30 mg/kg) and spironolactone (30 mg/kg) on the LS diet induced a biological picture of severe hypoaldosteronism and was not tolerated, whereas the HS diet prevented these abnormalities. The combination of FAD 286 A (30 mg/kg) and furosemide (30 mg/kg) on the HS diet corrected the diuretic-induced hypokalemia (4.1 +/- 0.2 versus 3.7 +/- 2.2 mEq/l, P < 0.033).
  
  
  CONCLUSIONS
  This experimental model will be useful to screen future aldosterone-synthase inhibitors and study their biological effects in various experimental conditions.
authors: INSERM U652, Paris, France. joelle.schlama@spim.jussieu.fr
authors: Joël
authors: J
authors: Ménard
authors: Marie-Françoise
authors: MF
authors: Gonzalez
authors: Thanh-Tam
authors: TT
authors: Guyene
authors: Alvine
authors: A
authors: Bissery