Abstract
Background Nitric oxide (NO) is a potent biological mediator and plays an important role in cardiovascular homeostasis. Here it activates the soluble guanylyl cyclase (sGC) that synthesizes cGMP. The intracellular second messenger cGMP regulates vascular tone, vascular permeability, modulates inflammation and platelet reactivity. In platelets cGMP activates platelet inhibitory pathways via PKG and thereby inhibits platelet activation. Many cardiovascular diseases e.g. pulmonary arterial hypertension (PAH), are associated to a defective NO signalling. Therefore agents that stimulate the sGC are interesting therapeutic tools for the treatment of several cardiovascular diseases. Riociguat (Bay 63-2561) stimulates the sGC NOindependently without the risk of nitrate tolerance. Clinical Phase II and III studies determined the efficacy and tolerability in pulmonary hypertension patients. Riociguat was well tolerated and also significantly improved exercise capacity and hemodynamic parameters. To further analyse the effects of riociguat on platelet activation we tested the inhibitory effects on functions in isolated platelets and whole blood to elucidate additional applications of riociguat and to estimate adverse effects such as increased bleeding tendencies.
Highlights
Nitric oxide (NO) is a potent biological mediator and plays an important role in cardiovascular homeostasis
Our results indicate that riociguat treatment will not lead to an increased bleeding tendency in pulmonary hypertension patients
In order to study the effects of riociguat on platelet soluble guanylyl cyclase (sGC) activity we monitored the VASP phosphorylation and cyclic nucleotides in washed platelets
Summary
Platelet inhibitory effects of the NO independent sGC stimulator riociguat (Bay 63-2561). Cora Reiss1*, Igor Mindukshev, Verena Bischoff, Stepan Gambaryan, Ulrich Walter. From 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Erfurt, Germany. From 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Erfurt, Germany. 28-30 June 2013
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