Role of nitric oxide in hemostatic system activation in vivo in humans.
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 NG-monomethyl L-arginine (L-NMMA 3mg/kg body weight i.v. over 5 minutes; n = 8), beta-Thromboglobulin (beta-TG), an indicator of platelet activity; prothrombin fragment 1 + 2 (F 1 + 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, beta-TG and F 1 + 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 beta-TG, F 1 + 2, and TxB2 levels in shed blood.(ABSTRACT TRUNCATED AT 250 WORDS)
Krejcy
K
K
Department of Clinical Pharmacology, University of Vienna, Austria.
Schmetterer
L
L
Kastner
J
J
Nieszpaur-Los
M
M
Monitzer
B
B
Schütz
W
W
Eichler
H G
HG
Kyrle
P A
PA
D000280:Administration, Inhalation; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001760:Bleeding Time; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D011516:Prothrombin / Q000032:analysis; D013929:Thromboxane B2 / Q000032:analysis; D001620:beta-Thromboglobulin / Q000032:analysis; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D001620:beta-Thromboglobulin; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013929:Thromboxane B2; D011516:Prothrombin; D001120:Arginine