NO donors and ACE inhibitors act in concert to inhibit human ACE activity and platelet aggregation in vitro
(English)Manuscript (preprint) (Other academic)
This study investigates the effects of exogenous and endogenous nitric oxide (NO) on human circulating and endothelial angiotensin-converting enzyme (ACE) activity, and platelet aggregation. The NO donor S-nitroso N-acetylpenicillamine SNAP (10-8-10-6 M) significantly and dose-dependently inhibited serum ACE activity. The concomitant addition of SNAP to ACE inhibitor-treated (captopril or enalaprilat) serum, further reduced ACE activity. In cultured endothelial cells from human umbilical veins (HUVEC), both SNAP and 3-morpholinosydnonimine (SIN-1) significantly reduced ACE activity. An additative effect was seen with a combined treatment of captopril and SNAP. Treatment with the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) did not affect ACE activity. Thrombin inhibited endothelial ACE activity, an effect that was abolished when cells were pretreated with L-NMMA. ADP-induced platelet aggregation was inhibited with SNAP, SIN-1 and nitroglycerine (GTN). Captopril did not affect aggregation, while a high concentration of enalaprilat (10-4 M) reduced it. The concomitant addition of 10-5 M ACE inhibitor to NO donor-treated platelets resulted in a further reduction of platelet aggregation. This effect was most evident with SIN-I and enalaprilat. In conclusion, both exogenous and endogenous NO inhibit human ACE activity. NO donors and ACE inhibitors act in concert to inhibit ACE and platelet aggregation.
angiotensin-converting enzyme, ACE inhibitors, HUVEC, nitric oxide, platelet aggregation
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-79493OAI: oai:DiVA.org:liu-79493DiVA: diva2:543045