Captopril decreases vascular reactivity independently of changes in converting enzyme activity and prostaglandin release in the rat isolated kidney.
The relationship of the vascular effect of captopril to angiotensin converting enzyme activity and prostaglandin-dependent mechanism was studied in rat isolated kidneys, perfused with Krebs-Henseleit at 20 ml/min per 2 kidneys, with basal perfusion pressures of 78 +/- 1 mm Hg (Mean +/- S.E.M.). Two doses of captopril were used; both low (0.05 microgram/ml) and high doses (5 microgram/ml) inhibited maximally the vasoconstrictor responses to 100 and 200 ng of angiotensin I. Captopril at the low dose did not affect the renal vasoconstrictor responses to norepinephrine (NE) (25-400 ng), whereas high-dose reduced the vasoconstriction to all doses of NE. Treatment with captopril tended to diminish dose-related release of prostaglandins in response to NE. Indomethacin (1 microgram/ml) prevented NE-induced release of bioassayable and radioimmunoassayable prostaglandins but did not affect the ability of captopril to reduce NE-induced vasoconstriction. High-dose captopril also decreased the vascular reactivity to angiotensin II (5 ng) and lysine vasopressin (10 mU); however, the renal vasoconstriction caused by PGE2 (80 ng) was unaffected by captopril. We conclude that high-dose captopril decreased vascular reactivity by a mechanism independent of converting enzyme inhibition and unrelated to a prostaglandin-dependent vascular mechanism.
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010477:Perfusion; D011392:Proline / Q000031:analogs & derivatives*; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D009638:Norepinephrine