title: Hypoxic pulmonary hypertension in chronic lung diseases: novel vasoconstrictor pathways.
abstract: Pulmonary hypertension is a well recognised complication of chronic hypoxic lung diseases, which are among the most common causes of death and disability worldwide. Development of pulmonary hypertension independently predicts reduced life expectancy. In chronic obstructive pulmonary disease, long-term oxygen therapy ameliorates pulmonary hypertension and greatly improves survival, although the correction of alveolar hypoxia and pulmonary hypertension is only partial. Advances in understanding of the regulation of vascular smooth muscle tone show that chronic vasoconstriction plays a more important part in the pathogenesis of hypoxic pulmonary hypertension than previously thought, and that structural vascular changes contribute less. Trials of existing vasodilators show that pulmonary hypertension can be ameliorated and systemic oxygen delivery improved in carefully selected patients, although systemic hypotensive effects limit the doses used. Vasoconstrictor pathways that are selective for the pulmonary circulation can be blocked to reduce hypoxic pulmonary hypertension without causing systemic hypotension, and thus provide potential targets for novel therapeutic strategies.
authors.affiliation: UCD School of Medicine, Conway Institute, Dublin, Ireland.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Rowan
authors.affiliation: UCD School of Medicine, Respiratory Medicine, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Keane
authors.affiliation: National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Seán
authors.initials: S
authors.lastname: Gaine
authors.affiliation: UCD School of Medicine, Conway Institute, Dublin, Ireland. Electronic address: paul.mcloughlin@ucd.ie.
authors.forename: Paul
authors.initials: P
authors.lastname: McLoughlin
mesh_terms: D002908:Chronic Disease; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008171:Lung Diseases / Q000150:complications / Q000503:physiopathology*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D044006:Receptors, Epoprostenol / Q000378:metabolism; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D044006:Receptors, Epoprostenol; D014665:Vasodilator Agents; D009569:Nitric Oxide; D054460:rho-Associated Kinases