Summary
There is a growing consensus that HPV is multi-factorial in mechanism, and, in particular, that for HPV to develop fully and be sustained there needs to be both a rise in VSM [Ca2+], initiated by mechanisms intrinsic to the VSM cell, and a concomitant increase in VSM Ca2+ sensitivity induced by an endothelium-derived mediator. The precise identity of the hypoxic sensor, the effector mechanisms leading to the rise in [Ca2+], and the endothelium-derived mediator remain however controversial. In terms of endothelium-dependent HPV, there is now fairly strong evidence that the RhoA/Rho kinase pathway is central to the hypoxia-induced Ca2+ sensitization, though other protein kinases may also be involved. Although this provides a potential therapeutic target for alleviation of both the detrimental effects of acute HPV in critically ill hypoxic patients, and pulmonary hypertension associated with chronic hypoxic lung disease, development of an antagonist to the putative endothelium-derived mediator would be a greater prize. However, the mediator must first be identified, and as yet no known endothelium-derived mediator has yet to be unequivocally demonstrated as essential for sustained HPV.
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Ward, J.P.T., Aaronson, P.I. (2004). Endothelium-dependent Hypoxic Pulmonary Vasoconstriction. In: Yuan, J.X.J. (eds) Hypoxic Pulmonary Vasoconstriction. Developments in Cardiovascular Medicine, vol 252. Springer, Boston, MA. https://doi.org/10.1007/1-4020-7858-7_12
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