title: Captopril decreases vascular reactivity independently of changes in converting enzyme activity and prostaglandin release in the rat isolated kidney.
abstract: 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.
mesh_terms: 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
chemical_list: D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D011392:Proline; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D009638:Norepinephrine