Nitric oxide-independent stimulation of soluble guanylate cyclase attenuates pulmonary fibrosis

Background Pulmonary fibrosis (PF) is an increasing cause of morbidity and mortality with five million people affected worldwide and a median survival time of less than three years. Effective anti-fibrotic agents for PF are currently lacking. The majority of patients with PF develop pulmonary hypertension (PH) and right heart failure. Impaired production of endogenous nitric oxide (NO) plays an important role in the pathogenesis of PF-associated PH. The NO signaling pathway involves activation of soluble guanylate cyclase (sGC) with subsequent generation of cGMP. We hypothesized that sGC might be involved in the pathogenesis of PF and that the NOindependent stimulation of sGC might attenuate PH and fibrotic changes in a clinically relevant mouse model of PF.