Nitric oxide donors and angiotensin-converting enzyme inhibitors act in concert to inhibit human angiotensin-converting enzyme activity and platelet aggregation in vitro.
This study investigates the effects of exogenous and endogenous nitric oxide (NO) on human circulating and endothelial angiotensin-converting enzyme activity and platelet aggregation. The NO donor S-nitroso-N-acetylpenicillamine (10(-8)-10(-6) M) significantly and dose-dependently inhibited serum angiotensin-converting enzyme activity. The concomitant addition of S-nitroso-N-acetylpenicillamine to angiotensin-converting enzyme inhibitor-treated (captopril or enalaprilat) serum, further reduced angiotensin-converting enzyme activity. In cultured endothelial cells from human umbilical veins (HUVECs), both S-nitroso-N-acetylpenicillamine and 3-morpholinosydnonimine (SIN-1) significantly reduced angiotensin-converting enzyme activity. An additative effect was seen with a combined treatment of captopril and S-nitroso-N-acetylpenicillamine. Treatment with the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) did not affect angiotensin-converting enzyme activity. Thrombin inhibited endothelial angiotensin-converting enzyme activity, an effect that was abolished when cells were pretreated with L-NMMA. Adenosine 5'-diphosphate (ADP)-induced platelet aggregation was inhibited with S-nitroso-N-acetylpenicillamine, SIN-1 and nitroglycerine. Captopril did not affect aggregation, while a high concentration of enalaprilat (10(-4) M) reduced it. The concomitant addition of 10(-5) M angiotensin-converting enzyme inhibitor to NO donor-treated platelets resulted in a further reduction of platelet aggregation. This effect was most evident with SIN-1 and enalaprilat. In conclusion, both exogenous and endogenous NO inhibit human angiotensin-converting enzyme activity. NO donors and angiotensin-converting enzyme inhibitors act in concert to inhibit angiotensin-converting enzyme and platelet aggregation.
Persson
K
K
Division of Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, SE-581 85, Linköping, Sweden. karin.persson@far.liu.se
Whiss
P A
PA
Nyhlén
K
K
Jacobsson-Strier
M
M
Glindell
M
M
Andersson
R G
RG
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015773:Enalaprilat / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D026423:S-Nitroso-N-Acetylpenicillamine; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D020030:Nitric Oxide Donors; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D002216:Captopril; D008981:Molsidomine; D007703:Peptidyl-Dipeptidase A; D010396:Penicillamine; D015773:Enalaprilat