Partial Blockade of Nitric Oxide Synthase Blunts the Exercise-induced Increase of von Willebrand Factor Antigen and of Factor VIII in Man

Abstract

SummaryBackground: Until now the effects of β-adrenergic agonists have largely been ascribed to their ability to induce intracellular formation of cyclic adenosine monophosphate. Recently evidence has been accumulating that at least some β1 and β2-adrenoceptor effects may be mediated by nitric oxide (NO). Based on these studies, we hypothesized that the β-adrenoceptor mediated increase of von Willebrand factor and factor VIII-activity (FVIII:C) in plasma during exercise, is caused by an NO-dependent mechanism. Methods: Thirteen young healthy subjects finished an exhaustive bicycle exercise protocol while they were infused placebo or the NO-synthase inhibitor N-monomethyl-L-arginine (L-NMMA) on two separate days in a randomized, double blind cross-over design. Findings: During exercise systemic haemo-dynamic changes were parallel in both treatment periods, but L-NMMA caused a partial inhibition of NO-synthase as evidenced by a 30% decrease in exhaled NO. The workload capacities were not different during L-NMMA or placebo infusion. However, under placebo treatment exercise increased vWF-Ag by a maximum of 61% (CI: 43-84; p = 0.002) and FVIII:C by 44% (CI: 31-59; p = 0.001), which was significantly attenuated when subjects were treated with L-NMMA (p <0.05): under L-NMMA treatment vWF-Ag increased by only 25% (CI: 5-51; p = 0.001) and FVIII:C by 12% (CI: 6-39; p = 0.001). Interpretation: Partial blockade of NO-synthase with L-NMMA blunts the exercise-induced increase in vWF-Ag and FVIII:C. Our trial points to a role of endogenous NO-generation in the β2-adrenergic increase in vWF/FVIII. Thus, we propose that physiologic processes which are induced by systemic β2-adrenoceptor stimulation may at least partly be mediated by NO.

The Effect of ABO Blood Group on von Willebrand Response to Exercise

“…The stimulus responsible for exercise-induced increases in plasma vWF content seems to be mediated by β-adrenergic receptors through a nitric oxide-dependent mechanism, and the hemostasis system could be conditioned by endothelial function. 13 Exercise-dependent effects on the coagulant activity of the FVIII-vWF complex have been studied through distinct protocols with different intensities and durations of exercise tests. Despite variations in the experimental protocols, all studies suggest significant increases of the coagulant activity.…”

Von Willebrand Factor in Cardiovascular Disease

“…VWF can be produced and released by endothelial cells by a variety of stimuli in vitro and in vivo such as hypoxia, 15 inflammatory cytokines, 16 thrombin, 17 leukocyte elastase, 18 histamine, 4 endotoxin, 19 exercise, 20 adrenaline, 21 and especially vasopressin. 22 Indeed, patients with von Willebrand disease are effectively treated with desmopressin, the synthetic analog of vasopressin, to raise their VWF levels.…”

Effects of physical activity on some of hemostatic parameters changes in epiphysectomized rats

“…Also, a recent study showed that anaerobic exercise accelerates blood coagulation and activates blood fibrinolytic activity (Ali and Hanachi, 2011). In this regard, if the stimulus responsible for exercise induced increase in plasma von Willebrand factor (vWF) and coagulation factor VIII (FIII), the content seems to be mediated by b-adrenergic receptors through a nitric oxide-dependent mechanism, where the haemostastic system could be conditioned by endothelial function and be modified during the aging process (Jilma et al, 1997). Also, based on one marathon study, despite increased levels of B-thromboglobulin, platelet aggregation was found to decrease after exercise (Rock et al, 1997).…”