Inhibition of the Renin-Angiotensin-System (RAS) in Rats with Hereditary Hypothalamic Diabetes Insipidus (DI)

Abstract

Experiments were carried out in DI rats in order to answer the following questions: 1) Does furosemide have an anti-diuretic action in DI rats? 2) Is the antidiuretic action due to a stimulation of the RAS? I) DI rats (n=10) were placed in metabolic cages. Saline (5 ml/kg) and furosemide (50 mg/kg) were injected intraperitoneally (i.p.). Cumulative urine volume (UV)(2 and 6 h after treatment) and urinary sodium excretion (UNa+)(6 h after treatment) were measured. Furosemide elicited an increase of UV during the first 2 h (21.4±0.7 vs 14.5±1.2 ml in controls) but a reduction of UV from the 2nd to the 6th h (5.1±1.2 vs 31.2±2.8ml). Total UV also decreased for the whole 6 h period in the furosemide treated rats (26.5±1.2 vs 45.7±3.8 ml). UNa+ was enhanced to 1336±72 vs 358±52 μEq by furosemide treatment. II) A converting enzyme inhibitor (SQ 14225, 2.5 mg/kg) was given orally in DI rats (n=9) in order to block the conversion of angiotensin I to angiotensin II. The experimental design was as described in I). SQ 14225 elicited an increase of UV 2 h (16.6±2.5 vs 8.3±1.5 ml) and 6 h (44.9±2.6 vs 28.8±1.6 ml) after treatment.