The effect of hydrogen peroxide on hypoxia, prostaglandin F2 alpha and potassium chloride induced contractions in isolated rat pulmonary arteries.
We have investigated the action of the product of the enzyme NADPH oxidase; hydrogen peroxide (H2O2), on the first phase of the hypoxic contraction, prostaglandin F2 alpha (PGF2 alpha)-induced contractions and potassium chloride (KCl)-induced contractions, in isolated rat pulmonary arteries in a wire myograph. Both concentrations of H2O2 (0.03 and 0.5 mM) produced initial contractions, and the higher concentration of H2O2 produced a significant inhibition of both the priming concentration of PGF2 alpha (5 microM) and the hypoxic contraction (P < 0.01 for both contractions). These effects were shown to be reversible, with contractions of a similar size to control values being seen to both PGF2 alpha (5 microM) and hypoxia following washout of H2O2 (P > 0.1 for both contractions). H2O2 (0.03 mM) was shown to have no significant effect upon either contraction (P > 0.1 for both contractions). H2O2 (0.5 mM) was also shown to have a significant inhibitory effect upon the efficacy (Emax) of the PGF2 alpha and KCl concentration-response curves (P < 0.01 for both contractions). This inhibition was again shown to be reversible. The higher concentration of H2O2 (0.5 mM) is clearly shown to be having a dual action, producing an initial contraction followed by inhibition of contractions to both PGF2 alpha and KCl. The mechanism by which H2O2 produces vasoconstriction is unclear, but it is suggested that H2O2 may inhibit the release of Ca2+ ions from intracellular stores as this is a common link between the modes of action of these two contractile agents. In addition to this, as an elevation in intracellular Ca2+ from intracellular stores appears to be a prerequisite for hypoxic pulmonary vasoconstriction (HPV), then this apparent mode of action of H2O2 could play an important role in the regulation of HPV and suggests a possible role for NADPH oxidase or a similar oxidoreductase as an oxygen sensor.
Jones
R D
RD
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, University of Sheffield, U.K.
Thompson
J S
JS
Morice
A H
AH
D000818:Animals; D015237:Dinoprost / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D011189:Potassium Chloride; D015237:Dinoprost; D006861:Hydrogen Peroxide