Effect of captopril or enalapril on renal prostaglandin E2.
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 PGE2 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 PGE2 excretion was determined. Renopapillary slices were obtained from some of the rats including controls and incubated to determine PGE2 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 PGE2 excretion increased 1.4-fold in response to C, but not to E. Papillary PGE2 synthesis demonstrated a marked decrease 2 h after in vivo administration of either ACEI compared to controls. However, when C or enalaprilat was added in vitro to renal slices obtained from controls, only C at 10(-5) M showed a significant 2-fold increase in renal PGE2 synthesis. These results suggest that (1) renal PGE2 synthesis may be dependent on circulating angiotensin II. (2) C, but not enalaprilat, has a direct stimulatory effect on renal PGE2 synthesis and (3) renal PGE2 may not be involved very much in the hypotensive effect of ACEI.
Katayama
S
S
Fourth Department of Medicine, Saitama Medical School, Japan.
Inaba
M
M
Maruno
Y
Y
Omoto
A
A
Itabashi
A
A
Kawazu
S
S
Ishii
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis* / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007679:Kidney Medulla / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D004656:Enalapril; D002216:Captopril; D012083:Renin; D015232:Dinoprostone