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. Copyright (C) 2000 Elsevier Science B.V.

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