Inhaled MK-5475 is proposed to directly stimulate soluble guanylate cyclase (sGC), independently of and synergistically with nitric oxide (NO), to increase levels of intracellular cyclic guanosine monophosphate (cGMP). Treatment with inhaled MK-5475 at 100 µg and 380 μg significantly reduced pulmonary vascular resistance (PVR) in participants with pulmonary arterial hypertension (PAH). Change in 6-min walk distance (6MWD) was not significant. Treatment with MK-5475 at all three doses was well tolerated. Error bars in graphs represent 95% confidence intervals. AE: adverse event; AEOI: adverse event of interest; GTP: guanosine triphosphate; PDE5: phosphodiesterase 5; SAE: serious adverse event.