Hydrogen peroxide--an intracellular signal in the pulmonary circulation: involvement in hypoxic pulmonary vasoconstriction.
Hypoxic pulmonary vasoconstriction (HPV) is a regulatory feature of the pulmonary circulation that ensures consistent matching of perfusion to ventilation in the normal lung. However, under pathophysiological conditions, HPV contributes to the elevated pulmonary arterial pressure inherent to numerous disease states. Consequently, control of HPV is an avenue of potential therapy for such conditions. This review discusses the role of hydrogen peroxide (H(2)O(2)) as an intracellular signal in the pulmonary circulation, concentrating on the potential involvement of H(2)O(2) in HPV and in the control of pulmonary arterial tone. Sites of hypoxic pulmonary arterial H(2)O(2) production include the mitochondrial electron transport chain, a microsomal electron transport chain containing an NADH oxidoreductase and alternatively, a membrane-bound NADPH oxidase. Each of these sources of H(2)O(2) and the effect of hypoxia on the production of reactive oxygen species are considered. The review also discusses the variance in vascular reactivity of H(2)O(2), which is described to elicit both pulmonary arterial vasoconstriction and dilatation at varying concentrations. The redox capabilities of H(2)O(2) are also considered. The relevance of all of these actions of H(2)O(2) are also assessed as potential pharmacological targets for the future development of therapy for lung diseases that are characterised by some degree of HPV and in the pathogenesis of pulmonary diseases in which reactive oxygen species are implicated.
Jones
R D
RD
Section of Respiratory Medicine, Academic Department of Medicine, The University of Hull, Castle Hill Hospital, Castle Road, Cottingham, East Yorkshire, HU16 5JQ, UK. r.d.jones@sheffield.ac.uk
Morice
A H
AH
D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D008171:Lung Diseases / Q000188:drug therapy / Q000503:physiopathology; D010084:Oxidation-Reduction; D011652:Pulmonary Circulation; D015398:Signal Transduction; D014661:Vasoconstriction; D014664:Vasodilation
D006861:Hydrogen Peroxide