Hypoxia, energy state and pulmonary vasomotor tone.
Vasomotor responses to hypoxia constitute a fundamental adaptation to a commonly encountered stress. It has long been suspected that changes in cellular energetics may modulate both hypoxic systemic artery vasodilatation (HSV) and hypoxic pulmonary artery vasoconstriction (HPV). Although limitation of energy has been shown to underlie hypoxic relaxation in some smooth muscles, the response to hypoxia in vascular smooth muscle does not appear to be a simple function of energy stores, but instead may involve perturbations of ATP or energy delivery to mechanisms controlling muscle force, and/or changes associated with anaerobic metabolism. Recent work in pulmonary vascular smooth muscle has demonstrated that energy stores are maintained during hypoxic pulmonary vasoconstriction, and that this is dependent on glucose availability and up-regulation of glycolysis. There is increasing evidence that glycolysis is preferentially coupled to a variety of membrane associated ATP dependent processes, including the Na(+) pump, Ca(2+)-ATPase, and possibly some protein kinases. These and other mechanisms may influence excitation-contraction coupling in both systemic and pulmonary arteries by effects on intracellular Ca(2+) and/or Ca(2+) sensitivity. Hypoxia has also been postulated to have major effects on other cytosolic second messenger systems including phosphatidylinositol pathways, cell redox state and mitochondrial reactive oxygen species production. This review examines the relationship between energy state, anaerobic respiration and hypoxic vasomotor tone, with a particular emphasis on hypoxic pulmonary vasoconstriction.
Department of Respiratory Medicine and Allergy, Centre for Cardiovascular Biology and Medicine, Guy's, King's and St Thomas' School of Medicine, King's College London, Guy's Campus, London SE1 9RT, UK. richard.leach@gstt.sthames.nhs.uk
Richard M
RM
Leach
Heidi S
HS
Hill
Vladimir A
VA
Snetkov
Jeremy P T
JP
Ward
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism*; D009129:Muscle Tonus / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology*