Mechanisms of hypoxic pulmonary vasoconstriction: can anyone be right?

Despite extensive studies over many years, there is still no real consensus regarding the mechanisms responsible for hypoxic pulmonary vasoconstrictio n (HPV). This is partially related to extensive variation between preparati ons. species, and the length of the hypoxic challenge, but also to an appar ent abundance of potential mechanisms. Whereas there is good evidence that hypoxia causes inhibition of K+ channels in pulmonary artery smooth muscle, with subsequent depolarisation and Ca2+ influx through voltage-activated C a2+ channels, there is also strong support for a critical role for Ca2+ rel ease from intracellular stores. Moreover other studies suggest that the end othelium provides an essential component of the overall response. We sugges t in this review that sustained HPV, as seen in the intact animal. is multi -factorial in origin and requires activation of more than one process for t he full response to develop. Fundamental issues that remain unresolved are outlined. (C) 1999 Elsevier Science B.V. All rights reserved.