The nitric oxide-soluble guanylate cyclase-cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase.

The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays a key role in the pathogenesis of pulmonary hypertension (PH). Targeted treatments include phosphodiesterase type 5 inhibitors (PDE5i) and sGC stimulators. The sGC stimulator riociguat is approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). sGC stimulators have a dual mechanism of action, enhancing the sGC response to endogenous NO and directly stimulating sGC, independent of NO. This increase in cGMP production

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Conflict of interest: R.L. Benza reports receiving grants from Actelion, Bayer AG, Bellerophon Therapeutics and Eiger Biopharmaceuticals. E. Grünig reports fees for lectures and/or consultations from Actelion, Bayer AG, GlaxoSmithKline, Merck Sharp & Dohme Corp., Pfizer and United Therapeutics outside the submitted work. P. Sandner and J.-P. Stasch are employees of Bayer AG, Wuppertal, Germany. G. Simonneau reports personal fees and nonfinancial support from Actelion, Bayer AG and Merck Sharp & Dohme outside the submitted work.