PARTIAL BLOCKADE OF NITRIC-OXIDE SYNTHASE BLUNTS THE EXERCISE-INDUCEDINCREASE OF VON-WILLEBRAND-FACTOR ANTIGEN AND OF FACTOR-VIII IN MAN

Background: Until now the effects of beta-adrenergic agonists have lar gely been ascribed to their ability to induce intracellular formation of cyclic adenosine monophosphate. Recently evidence has been accumula ting that at least some beta(1) and beta(2)-adrenoceptor effects may b e mediated by nitric oxide (NO). Based on these studies, we hypothesiz ed that the beta-adrenoceptor mediated increase of von Willebrand fact or and factor VIII-activity (FVIII:C) in plasma during exercise, is ca used by an NO-dependent mechanism. Methods: Thirteen young healthy sub jects 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-ove r design. Findings: During exercise systemic haemodynamic changes were parallel in both treatment periods, but L-NMMA caused a partial inhib ition of NO-synthase as evidenced by a 30% decrease in exhaled NO. The workload capacities were not different during L-NMMA or placebo infus ion. However, under placebo treatment exercise increased vWF-Ag by a m aximum 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 treate d with L-NMMA (p <0.05): under L-NMMA treatment vWF-Ag increased by on ly 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 th e exercise-induced increase in vWF-Ag and FVIII:C. Our trial points to a role of endogenous NO-generation in the beta(2)-adrenergic increase in vWF/FVIII. Thus, we propose that physiologic processes which are i nduced by systemic beta(2)-adrenoceptor stimulation may at least partl y be mediated by NO.