Aktivität und Bedeutung der erythrozytären NOS bei kardiovaskulären Risikofaktoren

In cardiovascular diseases changes in the metabolism of L-arginine-NO cause endothelial dysfunction with reduced bioavailability of NO. Besides endothelial cells, RBC also obtain an active NOS in the vascular system. NO synthesis by RBC-NOS is regulated by similar mechanism and modulates RBC deformability. It was unknown wether RBC-NOS activity is changed in cardiovascular diseases and wether these changes are involved in reduced RBC deformability. Until now, the influence of NO on microcirculation has been proved in vitro only. In this thesis, an in-vivo method was established to prove this influence. The results can be summarized as follows:- NO synthesis by RBC can be less stimulated in patients with cardiovascular risk factors.- One reason could be the increased activity of RBC arginase in patients with cardiovascular risk factors as proved in this thesis. Concerning the regulation of RBC-NOS activity by phosphorylation of serin 1177 no difference was found.- In patients with cardiovascular risk factors a tendency of a reduced basal RBC deformability was proved. Improvement of deformability in dependence of RBC-NOS activity was limited. - A microcirculation model of the chorioallantoic membran system of chicken embryos was established. Applying this model, it was possible to investigate in vivo RBC deformability and perfusion of the capillary system in dependence of NO. By interception of NO as well as by inhibition of NO synthesis RBC deformability was reduced and perfusion in microcirculation was disturbed.It seems that in cardiovascular diseases in analogy to endothelial L-arginine-NO metabolism also RBC L-arginine-NO metabolism is impaired. The changes in RBC NO synthesis could be relevant for microcirculation disorders. The effect of reduced bioavailability of NO on microcirculation was proved with an established in vivo microcirculation model. These investigations may serve as a basis for improvement of RBC NO synthesis as an approach in the treatment of microcirculation disorders in vascular diseases