The effect of diuretics can be limited by stimulation of counter-regulatory mechanisms, eventually leading to diuretic resistance. It is thought that the mineralocorticoid aldosterone might contribute to the development of diuretic resistance. To test this, we challenged genetically modified mice with or without a deletion of the gene coding for the aldosterone synthase (AS) with furosemide, hydrochlorothiazide (HCT) and triamterene. Urinary excretion was studied in metabolic cages
kidneys were studied for expression of sodium transporters. In both genotypes, a 4-day treatment with HCT via drinking water (400 mg/l) induced a similar natriuresis and modest loss of body weight <
10%. In contrast, furosemide (125 mg/l) and triamterene (200 mg/l) via drinking water stimulated a significantly higher natriuresis and body weight loss in AS