title: sGC stimulators: Evidence for riociguat beyond groups 1 and 4 pulmonary hypertension.
abstract: 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.
authors.affiliation: Advanced Heart Failure, Transplant, Mechanical Circulatory Support and Pulmonary Hypertension Section, Allegheny Health Network, Pittsburgh, PA, USA. Electronic address: Raymond.BENZA@ahn.org.
authors.forename: Raymond
authors.initials: R
authors.lastname: Benza
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Mathai
authors.affiliation: Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Vienna, VA, USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Nathan
mesh_terms: D002986:Clinical Trials as Topic; D020536:Enzyme Activators / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism*; D066253:Vascular Remodeling / Q000187:drug effects
chemical_list: D020536:Enzyme Activators; D011720:Pyrazoles; D011743:Pyrimidines; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat
keywords: NO-sGC-cGMP pathway; Pulmonary arterial hypertension; Riociguat; sGC stimulators