Effect of the converting enzyme inhibitor SQ-20881 on urinary excretion of prostaglandin E2 in the rat: influence of pretreatment with deoxycorticosterone.
The effect of SQ-20881, an inhibitor of the peptidyl dipeptidase that degrades kinins and converts angiotensin I to angiotensin II, on the urinary excretion of immunoreactive prostaglandin E2 (iPGE2) was studied in rats receiving either deoxycorticosterone (DOCA, 5 mg/day s.c.) or sesame oil vehicle for 10 days before and then during the study, DOCA-treated animals had higher urinary excretion of iPHE2 and kallikrein, and lower plasma renin, than did animals injected with oil only. In rats pretreated with DOCA, infusion of SQ-20881 (1.2 mg/day s.c.) for 6 days increased iPGE2 excretion from 87.3 +/- 1.9 to 150.9 +/- 14.5 ng/day (P < .05). In contrast, in rats pretreated with vehicle, SQ-20881 had no significant effect on urine iPGE2. The enzyme inhibitor did not affect the intake of fluid, the volume of urine or the urinary excretion of kallikrein and electrolytes in either DOCA- or vehicle-treated animals. The blood pressure reduction elicited by a bolus injection of bradykinin (1.0 microgram i.v.) was greater in rats receiving SQ-20881 than in vehicle-infused controls, both in the DOCA- and in the sesame oil-treated groups, suggesting inhibition of kinin degradation by the converting enzyme inhibitor. These results indicate that DOCA or the consequences of its administration are required for SQ-20881 to increase iPHE2 excretion in the rat. Such an effect of the inhibitor probably relates to stimulation of renal prostaglandin synthesis consequent to elevation of kinin levels.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011458:Prostaglandins E / Q000652:urine*; D051381:Rats; D012083:Renin / Q000032:analysis; D013722:Teprotide / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D011458:Prostaglandins E; D003900:Desoxycorticosterone; D013722:Teprotide; D012083:Renin; D001920:Bradykinin