Effect of captopril or enalapril on renal prostaglandin E 2

Abstract

Since one of the hypotensive mechanisms of angiotensin-converting enzyme inhibitor (ACEI) has been suggested to be mediated through the renal kinin-prostaglandin (PG) axis, the present study was designed to investigate the effect of captopril (C) or enalapril (E) on renal PGE 2 excretion or synthesis. Wistar male rats (BW 200–250 g) were given orally captopril at 30 mg/kg/day or enalapril at 10 or 30 mg/kg for one week. Before and after ACEI, blood pressure (tail cuff method) as well as PRA and urinary PGE 2 excretion was determined. Renopapillary slices were obtained from some of the rats including controls and incubated to determine PGE 2 synthesis. C or E administration resulted in a blood pressure decrease of 21 to 36 mm Hg with an increase in PRA. Urine volume and sodium excretion increased after daily treatment with C or E at 30 mg/kg. Urinary PGE 2 excretion increassed 1.4-fold in response to C, but not to E. Papillary PGE 2 synthesis demonstrated a marked decrease 2 h after i n v i v o administration of either ACEI compared to controls. However, when C or enalaprillat was added i n v i t r o to renal slices obtained from controls, only C at 10 −5 M showed a significant 2-fold increase in renal PGE 2 synthesis. These results suggest that (1) renal PGE 2 synthesis may be dependent on circulating angiotensin ∥, (2) C, but not enalaprilat, has a direct stimulatory effect on renal PGE 2 synthesis and (3) renal PGE 2 may not be involved very much in the hypotensive effect of ACEI.