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 oxid e (NO) on human circulating and endothelial angiotensin-converting enzyme a ctivity and platelet aggregation. The NO donor S-nitroso-N-acetylpenicillam ine (10(-8)-10(-6) M) significantly and dose-dependently inhibited serum an giotensin-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 enz yme activity. In cultured endothelial cells from human umbilical veins (HUV ECs), both S-nitroso-N-acetylpenicillamine and 3-morpholinosydnonimine (SIN -1) significantly reduced angiotensin-converting enzyme activity. An addita tive effect was seen with a combined treatment of captopril and S-nitroso-N -acetylpenicillamine. Treatment with the NO synthase inhibitor N-G-monometh yl-L-arginine (L- NMMA) did not affect angiotensin-converting enzyme activi ty. Thrombin inhibited endothelial angiotensin-converting enzyme activity, an effect that was abolished when cells were pretreated with L-NMMA. Adenos ine 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) re duced it. The concomitant addition of 10(-5) M angiotensin-converting enzym e inhibitor to NO donor-treated platelets resulted in a further reduction o f platelet aggregation. This effect was most evident with SIN-1 and enalapr ilat. In conclusion, both exogenous and endogenous NO inhibit human angiote nsin-converting enzyme activity. NO donors and angiotensin-converting enzym e inhibitors act in concert to inhibit angiotensin-converting enzyme and pl atelet aggregation. (C) 2000 Elsevier Science B.V. All rights reserved.