C57Bl/6N mice were subjected to transverse aortic constriction (TAC) for 6 weeks to induce left heart failure and secondary PH and were subsequently treated with either sildenafil (100 mg/kg/day) or riociguat (10 mg/kg/day) or placebo for 2 weeks.
Six weeks after surgery, TAC induced significant left ventricular hypertrophy and dysfunction associated with development of PH. Treatment with riociguat and sildenafil neither reduced left ventricular hypertrophy nor improved its function. However, both sildenafil and riociguat ameliorated PH, reduced pulmonary vascular remodeling and improved right ventricular function.
Thus, modulation of the NO–sGC–cGMP pathway by the PDE5 inhibitor sildenafil or sGC stimulator riociguat exerts direct beneficial effects on pulmonary hemodynamics and right ventricular function in the experimental model of secondary PH due to left heart disease and these drugs may offer a new therapeutic option for therapy of this condition.