Pulmonary Hypertension in High-Altitude Dwellers: Novel Mechanisms, Unsuspected Predisposing Factors
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Studies of high-altitude populations, and in particular of maladapted subgroups, may provide important insight into underlying mechanisms involved in the pathogenesis of hypoxemia-related disease states in general. Over the past decade, studies involving short-term hypoxic exposure have greatly advanced our knowledge regarding underlying mechanisms and predisposing events of hypoxic pulmonary hypertension. Studies in high altitude pulmonary edema (HAPE)-prone subjects, a condition characterized by exaggerated hypoxic pulmonary hypertension, have provided evidence for the central role of pulmonary vascular endothelial and respiratory epithelial nitric oxide (NO) for pulmonary artery pressure homeostasis. More recently, it has been shown that pathological events during the perinatal period (possibly by impairing pulmonary NO synthesis), predispose to exaggerated hypoxic pulmonary hypertension later in life. In an attempt to translate some of this new knowledge to the understanding of underlying mechanisms and predisposing events of chronic hypoxic pulmonary hypertension, we have recently initiated a series of studies among high-risk subpopulations (experiments of nature) of high-altitude dwellers. These studies have allowed to identify novel risk factors and underlying mechanisms that may predispose to sustained hypoxic pulmonary hypertension. The aim of this article is to briefly review this new data, and demonstrate that insufficient NO synthesis/bioavailability, possibly related in part to augmented oxidative stress, may represent an important underlying mechanism predisposing to pulmonary hypertension in high-altitude dwellers.
KeywordsNitric Oxide Pulmonary Hypertension Down Syndrome Hypoxic Pulmonary Vasoconstriction Hypoxic Pulmonary Hypertension
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- 2.Barker DJP. Mothers, babies, and disease in later life. London: BMJ Books, 1994.Google Scholar
- 12.de Haan JB, Susil B, Pritchard M, and Kola I. An altered antioxidant balance occurs in Down syndrome fetal organs: implications for the “gene dosage effect” hypothesis. J Neural Transm Suppl: 67–83, 2003.Google Scholar
- 26.Joanny P, Steinberg J, Robach P, Richalet JP, Gortan C, Gardette B, and Jammes Y. Operation Everest III (Comex’97): the effect of simulated sever hypobaric hypoxia on lipid peroxidation and antioxidant defence systems in human blood at rest and after maximal exercise. Resuscitation 49: 307–314, 2001.PubMedCrossRefGoogle Scholar
- 39.Sartori C, Turini P, Allemann Y, Salinas C, Rodriguez A, Hutter D, Thalmann S, Villena M, and Scherrer U. Protective effect of female sex hormones against pulmonary hypertension in bolivian high altitude natives. High Altitude Medicine and Biology 3: A430, 2003.Google Scholar
- 45.Smith APL, Emery CJ, and Higenbottam TW. Perinatal chronic hypoxia decreases endothelial nitric oxide synthase (NOS III) and increases preproendothelin-1 (ppET-1) mRNA levels in rat. Eur Respir J 10: 433s (Abstract), 1997.Google Scholar
- 47.Thalmann S, Allemann Y, Jayet PY, Hutter D, Salinas C, Stuber T, Shaw S, Villena M, Sartori C, and Scherrer U. Oxidative stress mediated chronic pulmonary hypertension in re-entry pulmonary edema-prone high altitude dwellers. FASEB J 19(5): A1333, 2005.Google Scholar
- 48.Ward MP, Milledge JS, and West JB. High Altitude Medicine and Physiology. Philadelphia: University of Pennsylvania Press, 1989.Google Scholar