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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:2063-2067.)
© 1995 American Heart Association, Inc.

Articles

Role of Nitric Oxide in Hemostatic System Activation In Vivo in Humans

Kurt Krejcy; Leopold Schmetterer; Johannes Kastner; Malgorzata Nieszpaur-Los; Brigitte Monitzer; Wolfgang Schütz; Hans-Georg Eichler; Paul A. Kyrle

From the Department of Clinical Pharmacology (K.K., L.S., J.K., B.M., H.-G.E.), Institute of Pharmacology (K.K., W.S.), Department of Internal Medicine I, Division of Hematology and Hemostaseology (M.N.-L., P.A.K.), University of Vienna, Vienna, Austria.

Correspondence to Kurt Krejcy, MD, Department of Clinical Pharmacology, Vienna University Hospital, Allgemeines Krankenhaus Wien, A-1090 Wien, Währinger Gürtel 18-20, Austria.

Abstract NO is a potent inhibitor of in vitro platelet aggregation and adhesion. In view of possible future widespread use of NO in pulmonary and cardiovascular diseases, we investigated the role of NO in hemostatic system activation in vivo in humans. Sixteen healthy male volunteers (age range, 22 to 33 years) received either NO by inhalation (50 ppm over 30 minutes; n=8) or the NO synthase inhibitor N^G-monomethyl L-arginine (L-NMMA 3 mg/kg body weight IV over 5 minutes; n=8). ß-Thromboglobulin (ß-TG), an indicator of platelet activity; prothrombin fragment 1+2 (F₁₊₂), an index of coagulation activation; and thromboxane B₂ (TxB₂), a measure of platelet prostaglandin synthesis, were determined in blood samples obtained from bleeding-time incisions ("shed blood") at baseline and after administration of the respective drug. In addition, ß-TG and F₁₊₂ were also determined in venous blood. To verify the systemic effects of the drugs, methemoglobin and plasma nitrites/nitrates were measured in the NO group, and cardiac output and exhaled NO were measured in the L-NMMA group. Compared with baseline, methemoglobin and plasma nitrates increased by 73±12% (P=.006) and 60±9% (P<.001), respectively, following NO inhalation. L-NMMA infusion resulted in decreases in both cardiac output (by 16±2%; P<.001) and exhaled NO (by 54±7%; P<.001). NO inhalation or L-NMMA infusion had no significant effect on ß-TG, F₁₊₂, and TxB₂ levels in shed blood. No significant changes in platelet counts and levels of coagulation activation markers were found in venous blood after drug administration. In contrast to the in vitro data, neither inhalation of NO nor inhibition of NO synthesis by infusion of L-NMMA had a major impact on hemostatic system activation in vivo in healthy individuals.

Key Words: NO inhalation • L-NMMA • bleeding time • hemostatic system activation

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