title: Riociguat for the treatment of pulmonary hypertension.
abstract: Nitric oxide (NO) is a critical signaling molecule in the pulmonary vasculature. NO activates soluble guanylate cyclase (sGC) resulting in the synthesis of cyclic guanosine monophosphate (cGMP) - a key mediator of pulmonary artery vasodilatation that may also inhibit smooth muscle proliferation and platelet aggregation. Pulmonary hypertension, a serious, progressive and often fatal disease is characterized by NO-sGC-sGMP pathway dysregulation. Riociguat is a member of a novel therapeutic class known as soluble guanylate stimulators. Riociguat has a dual mode of action, acting in synergy with endogenous NO and also directly stimulating sGC independently of NO availability. Phase 3 randomized control trials have demonstrated that riociguat improves clinical, physiologic and hemodynamic parameters in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. In this review we will discuss the pharmacologic properties of riociguat and its appropriate implementation into clinical practice.
authors.affiliation: a Division of Respirology , Firestone Institute for Respiratory Health, McMaster University , Hamilton , Canada.
authors.forename: Nathan
authors.initials: N
authors.lastname: Hambly
authors.affiliation: a Division of Respirology , Firestone Institute for Respiratory Health, McMaster University , Hamilton , Canada.
authors.forename: John
authors.initials: J
authors.lastname: Granton
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008168:Lung / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase
chemical_list: D000959:Antihypertensive Agents; D011720:Pyrazoles; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C542595:riociguat
keywords: chronic thromboembolic pulmonary hypertension; pulmonary arterial hypertension; pulmonary hypertension; riociguat; soluble guanylate cyclase