A comparison of the antiplatelet effect of S-nitrosoglutathione in whole blood and platelet-rich plasma.
Journal - Thrombosis research (United States )
|ISSN : ||0049-3848|
|Mesh Heading : ||Adenosine Diphosphate Blood Platelets Female Fibrinogen Flow Cytometry Humans Male Nitric Oxide P-Selectin Platelet Activation Platelet Aggregation Inhibitors S-Nitrosoglutathione pharmacology metabolism metabolism pharmacology metabolism drug effects|
|Mesh Heading Relevant : ||Platelet Transfusion pharmacology blood pharmacology|
Neither endogenous nor inhaled nitric oxide influences the function of circulating platelets in healthy volunteers.
Journal - Clinical science (London, England : 1979) (ENGLAND )
Experimental models have indicated prothrombotic effects of inhibition of nitric oxide (NO) production, and anti-thrombotic effects of inhaled NO, but the influence of NO on platelet function in vivo in humans is not well established. We therefore investigated the effects of systemic inhibition of NO synthesis by N(G)-monomethyl-L-arginine (L-NMMA) and of NO inhalation on platelet function in vivo. On two occasions, L-NMMA (13.5 mg/kg) or saline infusion was administered to 14 healthy volunteers in a double-blind cross-over study. After a 30 min infusion of L-NMMA or placebo, NO inhalation (30 p.p.m) was added during the remaining 30 min of infusion, on both occasions. Measurements included filtragometry ex vivo (reflecting platelet aggregability), flow-cytometric evaluation of platelets in whole blood (fibrinogen binding and P-selectin expression), plasma beta-thromboglobulin (reflecting platelet secretion), cGMP in platelets and plasma, thrombin generation markers (thrombin fragment 1+2 and thrombin-antithrombin complexes) in plasma, and bleeding time. L-NMMA increased blood pressure and decreased heart rate. NO inhalation did not influence blood pressure or heart rate, but caused a 3-fold elevation in plasma cGMP levels (P<0.001). Neither L-NMMA nor NO influenced filtragometry readings or flow-cytometric determinations of platelet fibrinogen binding and P-selectin expression. Furthermore, plasma beta-thromboglobulin, platelet cGMP and thrombin generation markers were not influenced by either treatment. Bleeding time was not influenced by L-NMMA compared with placebo, but was increased by approximately 25% during NO inhalation (P<0.01), whether NO synthesis had been inhibited or not. The prolongation of bleeding time by inhaled NO was not accompanied by any effect on the platelet variables assessed. The present results indicate that circulating platelets are not influenced by endogenous or inhaled NO, presumably due to the rapid inactivation of NO in the blood. This does not exclude possible effects of endothelial NO in the interface between the blood and the vessel wall.
|ISSN : ||0143-5221|
|Mesh Heading : ||Adult Bleeding Time Blood Platelets Cross-Over Studies Cyclic GMP Double-Blind Method Enzyme Inhibitors Flow Cytometry Hemodynamics Humans Leukocyte Count Male Nitric Oxide Nitric Oxide Synthase Platelet Count Thrombin omega-N-Methylarginine drug effects metabolism blood pharmacology drug effects drug effects pharmacology antagonists & inhibitors drug effects biosynthesis pharmacology|
|Mesh Heading Relevant : ||physiology physiology|