Differing effects of two angiotensin converting enzyme inhibitors, captopril and CI-906, on diuresis and the urinary excretion of kallikrein and prostaglandins in spontaneously hypertensive rats.
The effects of two angiotensin I converting enzyme inhibitors on the kallikrein-kinin system and prostanoids were studied in spontaneously hypertensive rats. The doses of captopril were 20, 50 and 100 mg/kg X day given twice daily, and those of CI-906 20 and 40 mg/kg once daily. Both drugs were equally effective in reducing the systolic blood pressure. Captopril increased urine volume dose-dependently (up to 3-fold with the largest dose). Only the larger dose of CI-906 was slightly diuretic. Captopril decreased the 24-h urinary excretion of kallikrein, while the excretion of the prostacyclin metabolite 6-keto-PGF1 alpha was increased markedly and that of T X B2 to a lesser extent. CI-906 had no effect on the 24-h urinary excretion of kallikrein, 6-keto-PGF1 alpha and T X B2. Both drugs tended to reduce PGE2 excretion. Captopril and CI-906 did not alter plasma kininogen levels. The marked renal effects of captopril may be caused by a strong local inhibition of converting enzyme in the kidneys. Captopril is mainly excreted unchanged in urine, and it is secreted actively by the proximal tubular cells. CI-906 is eliminated predominantly by biliary excretion. It is also possible that direct stimulation of prostacyclin formation by captopril may be involved in the diuretic action of the drug. However, as it was shown with CI-906, the increase in urine flow and the associated changes in urinary kallikrein and prostanoids are not necessary for the antihypertensive effect caused by the inhibition of converting enzyme.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D015232:Dinoprostone; D004231:Diuresis / Q000187:drug effects*; D006973:Hypertension / Q000652:urine*; D007546:Isoquinolines / Q000494:pharmacology*; D007610:Kallikreins / Q000652:urine*; D011392:Proline / Q000031:analogs & derivatives*; D011453:Prostaglandins / Q000652:urine*; D011458:Prostaglandins E / Q000652:urine; D000077583:Quinapril; D051381:Rats; D044005:Tetrahydroisoquinolines; D013929:Thromboxane B2 / Q000652:urine
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D011453:Prostaglandins; D011458:Prostaglandins E; D044005:Tetrahydroisoquinolines; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D011392:Proline; D002216:Captopril; D007610:Kallikreins; D015232:Dinoprostone; D000077583:Quinapril