Endothelium-derived mediators and hypoxic pulmonary vasoconstriction.
The vascular endothelium synthesises, metabolises or converts a multitude of vasoactive mediators, and plays a vital role in the regulation of pulmonary vascular resistance. Its role in hypoxic pulmonary vasoconstriction (HPV) is however controversial. Although HPV has been demonstrated in both pulmonary arteries where the endothelium has been removed and isolated pulmonary artery smooth muscle cells, many reports have shown either partial or complete dependence on an intact endothelium for sustained HPV (> approximately 20 min). However, despite many years of study no known endothelium-derived mediator has yet been unequivocally shown to be essential for HPV, although several may either facilitate the response or act as physiological brakes to limit the extent of HPV. In this article we review the evidence for and against the role of specific endothelium-derived mediators in HPV. We make the case for a facilitatory or permissive function of the endothelium, that in conjunction with a rise in smooth muscle intracellular Ca(2+) initiated by a mechanism intrinsic to smooth muscle, allows the development of sustained HPV. In particular, we propose that in response to hypoxia the pulmonary vascular endothelium releases an as yet unidentified agent that causes Ca(2+) sensitisation in the smooth muscle.
Department of Respiratory Medicine and Allergy, Centre for Cardiovascular Biology and Medicine, Guy's, King's and St Thomas' School of Medicine, 5th Floor Thomas Guy House, King's College London, Guy's Campus, London SE1 9RT, UK.
Philip I
PI
Aaronson
Thomas P
TP
Robertson
Jeremy P T
JP
Ward
D000818:Animals; D015777:Eicosanoids / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D011652:Pulmonary Circulation / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D015777:Eicosanoids; D016232:Endothelins; D009569:Nitric Oxide