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• W1990476634 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). Conclusion This experimental model will be useful to screen future aldosterone-synthase inhibitors and study their biological effects in various experimental conditions." @default.
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• W1990476634 date "2006-06-01" @default.
• W1990476634 modified "2023-10-13" @default.
• W1990476634 title "Investigation of aldosterone-synthase inhibition in rats" @default.
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• W1990476634 doi "https://doi.org/10.1097/01.hjh.0000226205.65442.f2" @default.
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