The potentiation of the nitric oxide (NO) pathway has formed one of the cornerstones of pulmonary hypertension (PH) treatment for the last~20 years.1 First used were phosphodiesterase type 5 (PDE5) inhibitors, which reduce the breakdown of cyclic GMP (cGMP), one of the key endpoints of the NO pathway. The subsequent increase in cGMP levels leads to increased protein kinase G causing pulmonary vascular smooth muscle relaxation and potential anti-remodelling effects. The efficacy of PDE5 inhibition remains dependent on the endogenous formation of NO to activate soluble guanylate cyclase (sGC), with consequent production of cGMP, which limits potential efficacy in PH where endogenous NO is known to be deficient.2 Instead, sGC stimulators are able to increase cGMP production, even in conditions of NO deficiency or absence, by directly stimulating heme-containing sGC and by stabilising NO binding to sGC, making sGC more responsive to endogenous NO.2…
