SGC stimulators: Evidence for riociguat beyond groups 1 and 4 pulmonary hypertension

Raymond Benza, Stephen Mathai, Steven D. Nathan

Research output: Contribution to journalArticle


Pulmonary hypertension (PH) is a chronic cardiopulmonary disorder that if left untreated, progresses rapidly and is ultimately fatal. The World Health Organization (WHO) has classified PH into 5 distinct groups according to pathophysiology, hemodynamic characteristics, and clinical presentation. Dysfunction in the nitric oxide (NO) pathway plays a key role in the pulmonary hypertension disease process, including in WHO Groups 2 and 3 PH. PH is associated with endothelial dysfunction, impaired synthesis of NO, and insufficient stimulation of the NO-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway, which reduces cGMP production. cGMP regulates vascular tone, cellular proliferation, inflammation, and fibrosis and its depletion can lead to a variety of abnormalities, including pulmonary vasoconstriction, impaired vascular remodeling, and in situ thrombosis. This review will examine a novel class of drugs called sGC stimulators which directly stimulate sGC independently of NO, leading to increased production of cGMP.

Original languageEnglish (US)
JournalRespiratory Medicine
Publication statusAccepted/In press - Jun 15 2016



  • NO-sGC-cGMP pathway
  • Pulmonary arterial hypertension
  • Riociguat
  • SGC stimulators

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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