Role of renal prostaglandins in the action of ramipril (HOE-498) in normotensive rats.
Changes in blood pressure, plasma renin activity, urine volume, urinary PGE2, 6-keto-PGF1 alpha and kinins, were studied after the administration of the angiotensin converting enzyme inhibitor ramipril (100 mu/kg/day), for one week in concomitantly indomethacin (1 mg/kg/day) treated and untreated rats. Measurements were made basally, before Ramipril administration and on days 1 and 7 during the treatment. Ramipril given alone induced a decrease in urinary PGE2 (NS) and 6-keto-PGF1 alpha (p less than 0.05) on day 1, together with an increase in urinary kinins on day 7 (p less than 0.01) and in urine volume on days 1 and 7 (p less than 0.05). Increased urinary PGE2 (NS) and 6-keto-PGF1 alpha (p less than 0.05) were observed in indomethacin pretreated rats after ramipril administration. No modifications in BP levels were observed either with indomethacin or with ramipril given alone or with ramipril plus indomethacin. Ramipril increased plasma renin activity levels both in indomethacin treated and untreated rats on days 1 (p less than 0.01) and 7 (p less than 0.05). The diuretic effect of ramipril and the stimulation of kinins were blunted when concomitant indomethacin was administered. Although a stimulatory effect of ramipril on urinary PGS was only observed during indomethacin administration, the present results would suggest that a non-inhibited PGS synthesis would be required for the renal actions of Ramipril.
Lahera
V
V
Departamento de Fisiologia, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Durán
F
F
Cachofeiro
V
V
Cañizo
F J
FJ
Cantón
J J
JJ
Rodriguez
F J
FJ
Tresguerres
J A
JA
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D015232:Dinoprostone / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007705:Kinins / Q000652:urine; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D017257:Ramipril; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D007705:Kinins; D011453:Prostaglandins; D015121:6-Ketoprostaglandin F1 alpha; D012083:Renin; D015232:Dinoprostone; D017257:Ramipril