Nitric oxide and other novel therapies for pulmonary hypertension.
Pulmonary hypertension is an uncommon, yet devastating, syndrome with a complex underlying pathobiology. Hypoxia, inflammation, and increased shear stress appear to be the primary pathogenic events; however, mechanisms by which these processes lead to pulmonary hypertension remain incompletely understood. The ultimate increase in pulmonary vascular resistance is attributed to remodelling of the walls of resistance vessels, which can lead to encroachment on and reduction of the vascular lumen. The number of blood vessels per unit of cross-sectional area in the hypertensive lung is also reduced, which can contribute to increased vascular resistance. Regardless of its etiology, endothelial dysfunction underlies pulmonary hypertension, one manifestation of which is the attenuated production of bioactive nitric oxide. Nitric oxide administration can exert beneficial effects at various stages of the disease. Here we review the known pathobiology of pulmonary hypertension, with a principal focus on endothelial nitric oxide, and also summarize the data on nitric oxide replacement therapy and other novel therapies that relate to nitric oxide as one approach to treatment.
Napoli
Claudio
C
Department of Medicine, University of Naples, Naples, Italy.
Loscalzo
Joseph
J
D000280:Administration, Inhalation; D015687:Cell Hypoxia; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology*; D009569:Nitric Oxide / Q000494:pharmacology / Q000627:therapeutic use*; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D016166:Free Radical Scavengers; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate