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lüll Mechanisms of hypoxic pulmonary vasoconstriction and their roles in pulmonary hypertension: new findings for an old problem Ward JP; McMurtry IFCurr Opin Pharmacol 2009[Jun]; 9 (3): 287-96Hypoxic pulmonary vasoconstriction (HPV) normally optimises ventilation-perfusion matching in the lung, but leads to pulmonary hypertension (PH) under conditions of global hypoxia. The past few years have provided some major advances in our understanding of this complex phenomenon, but significant controversy remains concerning many of the key underlying mechanisms. On balance, recent evidence is most consistent with an elevation in mitochondria-derived reactive oxygen species as a key event for initiation of HPV, with consequent Ca2+ release from intracellular ryanodine-sensitive stores, although the activation pathways and molecular identity of the associated Ca2+ entry pathways remain unclear. Recent studies have also raised our perception of the critical role played by Rho kinase (ROCK) in both sustained HPV and the development of PH, further promoting ROCK and the pathways regulating its activity and expression as important therapeutic targets.|*Vasoconstriction[MESH]|Animals[MESH]|Calcium/metabolism[MESH]|Drug Delivery Systems[MESH]|Humans[MESH]|Hypertension, Pulmonary/drug therapy/etiology/*physiopathology[MESH]|Hypoxia/*physiopathology[MESH]|Potassium Channels, Voltage-Gated/metabolism[MESH]|rho-Associated Kinases/metabolism[MESH] |