Interactions between muzolimine, PgE2 and the renin-angiotensin-aldosterone system

The aim of our study was to determine the possible interrelation between muzolimine and the renal PG and renin-angiotensin systems by direct assay of these renal hormones. 4 groups of five rats were subdivided as follows: Group 1: controls; Group 2: rats treated with muzolimine (100 mg/kg); Group 3: rats treated with indomethacin (4 mg/kg); Group 4: rats treated with both muzolimine and indomethacin. After 3 days, the rats were transferred to metabolic cages, urine and plasma samples were taken on the 4th day and the following parameters assayed: Urine: creatinine, Na+, PGE2. Plasma: PRA and aldosterone.

Muzolimine: 1) increase PRA (11.8 +/- 1.06 vs. 8.66 +/- 1.56 AI ng/ml/h - p less than 0.01) and 2) increases PGE2 release (7.08 +/- 3.22 vs. 0.6 +/- 0.19 micrograms/mg urine creatinine - p less than 0.005). PG synthesis-inhibition (indomethacin) lowers (0.118 +/- 0.056 mmol Na+/mg urine creatinine of group 2 vs 0.043 +/- 0.019 mmol Na+/mg urine creatinine of group 4 - p less than 0.025) although not completely abolishes (0.043 +/- 0.019 nmol Na+/mg urine creatinine of group 4 vs. 0.019 +/- 0.006 mmol Na+/mg of group 3 - p less than 0.05) the natriuretic effect of muzolimine. This suggests that the natriuretic activity of the drug, at least in part, depends on PGE2 production.