Hypoxic Pulmonary Hypertension, Novel Predisposing Factors, Unsuspected Mechanisms

Urs Scherrer, Emrush Rexhaj, Stefano. F. Rimoldi, Yves Allemann, Claudio Sartori

Abstract

High altitude constitutes an exciting natural laboratory for medical research. Over the past decade, high-altitude studies have provided important new insight into the regulation of the pulmonary circulation. 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 for pulmonary artery pressure homeostasis. Studies of healthy and maladapted high-altitude dwellers have provide important new insight into mechanisms conferring protection against/predisposing to pulmonary hypertension. Finally, the ambient hypoxia associated with high-altitude exposure facilitates the detection of pulmonary (and systemic) vascular dysfunction at an early stage. Here, we will summarize recent studies that, by capitalizing on these observations, have led to the description of novel mechanisms underpinning pulmonary hypertension and to the first direct demonstration of fetal programming of pulmonary vascular dysfunction in humans.

Keywords: Fetal programming, high altitude, hypoxia, nitric oxide, oxidative stress, pulmonary hypertension

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