Nitric oxide modulates captopril-mediated angiotensin-converting enzyme inhibition in porcine iliac arteries.
The influence of the angiotensin-converting enzyme inhibitor captopril on bradykinin-and angiotensin I-induced responses with special regard to nitric oxide (NO) was studied. Auxometric tension and angiotensin-converting enzyme activity was studied in isolated porcine iliac arteries. Captopril potentiated bradykinin-induced contraction of preparations with intact endothelium; this potentiation was not seen with the kininase I inhibitor mergepta or a bradykinin B(1)-receptor antagonist. Captopril did not affect bradykinin-induced relaxation. The captopril-mediated increase of bradykinin-induced contraction was only seen in preparations with intact endothelium, while captopril did not affect arterial strips treated with Nomega-nitro-L-arginine. Angiotensin I-induced contractions was less reduced by captopril when the strips were pretreated with Nomega-nitro-L-arginine. Both captopril and the NO donor S-nitroso-N-acetyl-penicillamine inhibited angiotensin-converting enzyme activity. An additional reduction in angiotensin-converting enzyme activity was seen when S-nitroso-N-acetyl-penicillamine was added to captopril-treated preparations. In conclusion, captopril increased bradykinin-induced contraction in a NO-dependent manner. This potentiation is probably mediated by the increased metabolism of bradykinin by kininase I, and the additive angiotensin-converting enzyme inhibitory effect of captopril and NO.
Persson
K
K
Division of Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, S-581 85, Linköping, Sweden. karin.persson@far.liu.se
Andersson
R G
RG
D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007083:Iliac Artery / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D019335:Nitroarginine; D009569:Nitric Oxide; C029729:2-mercaptomethyl-3-guanidinoethylthiopropionic acid; D026423:S-Nitroso-N-Acetylpenicillamine; D000803:Angiotensin I; D002216:Captopril; D015097:3-Mercaptopropionic Acid; D007703:Peptidyl-Dipeptidase A; D010396:Penicillamine; D001920:Bradykinin