Decreased vascular responsiveness produced by angiotensin-converting enzyme inhibitors in the rat isolated kidney.
The effects of three angiotensin converting enzyme (ACE) inhibitors - captopril, MK-421 diacid, and teprotide - on renal vascular responses to graded (50, 100, 200 ng) injections of norepinephrine (NE) were examined in rat isolated perfused kidneys, having a mean basal perfusion pressure of 78 +/- 10 mm Hg. The minimum dose of captopril (0.05 microgram/ml, low dose) that abolished the vasoconstrictor responses to 100 and 200 ng angiotensin I did not affect NE-induced renal vasoconstriction, whereas a dose 100 times greater (high-dose captopril, 5 micrograms/ml) reduced the vasoconstrictor action of NE. MK-421 diacid also at high dose (1 microgram/ml), caused similar reduction in renal vasoconstrictor responses to NE. In contrast, a high dose of teprotide (50 micrograms/ml) did not affect renal vascular responsiveness to NE. The threshold dose of NE that released prostaglandins, measured by bioassay, was 50 ng. Indomethacin (1 microgram/ml) prevented NE-induced release of prostaglandins but did not affect the ability of captopril to attenuate NE-induced vasoconstriction. We conclude that captopril and MK-421 diacid decreases vascular reactivity in the rat isolated kidney by a mechanism independent of ACE inhibition and unrelated to a prostaglandin-dependent vascular mechanism. Moreover, the presence of mercapto function in the ACE inhibitor is not essential since captopril, which has a sulfhydryl group, and MK-421 diacid, which lacks this group, have similar effects on renal vascular responsiveness.
D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004656:Enalapril; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013722:Teprotide / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D011453:Prostaglandins; D004656:Enalapril; D000803:Angiotensin I; D002216:Captopril; D013722:Teprotide; D009638:Norepinephrine; D007213:Indomethacin