Discussion
Infusion of 100 µg/kg Riociguat gave modest systemic vasodilatation seen as a drop in coronary and systemic vascular resistance of 36% and 26%, respectively. Right and left ventriculoarterial coupling index (Ees/Ea), stroke work efficiency (SWeff), and the relationship between left ventricular myocardial oxygen consumption (MVO2 ) and total mechanical work (pressure-volume area; PVA) were unaffected by Riociguat. In contrast, systemic and pulmonary vasoconstriction induced by L-NAME (15 mg/kg) shifted the Ees/Ea ratio toward reduced SWeff in both systemic and pulmonary circulation. However, there was no surplus oxygen consumption, that was measured by the MVO2 /PVA relationship after L-NAME in Riociguat-treated pigs. This suggests that Riociguat can reduce the NO-related cardiometabolic inefficiency previously observed by blocking the NO pathway.