Low concentrations of reactive oxygen species cause vasoconstriction of small distal pulmonary arteries.

Controversy rages as to the role of mitochondria-derived reactive oxygen species (ROS) in hypoxic pulmonary vasoconstriction. As a basic premise, exogenous ROS should mimic hypoxia if an elevation in ROS underlies HPV, but cause dilatation (or do nothing) if HPV is initiated by a fall in ROS. Although H2O2 has been shown to constrict pulmonary artery, this was for concentrations far higher (mM) than physiological levels. We therefore examined low concentrations of H2O2 and menadione, which increases ROS generation primarily by mitochondria, on rat small intrapulmonary arteries (IPA). 10–100μM H2O2 caused vasoconstriction, with a large transient and small sustained component. At 30μM H2O2 the transient was 10 ± 3% of 80mM KCl induced tension (KPSS), and the sustained constriction 4 ± 1% (n=11). Menadione caused a sustained constriction, reaching 6 ± 3% KPSS at 8μM (n=5). These constrictions are small, but HPV is potentiated by pretone. We therefore examined this for H2O2 and menadione. Pretone (~15% KPSS) induced by 27mM [K+] significantly potentiated H2O2-induced transient constrictions (to 51 ± 7% KPSS, n=7, p<0.001), and induced by PGF2α significantly potentiated menadione-induced constriction (47 ± 4% KPSS, n=8, p<0.001). Constriction to either agent was only partially suppressed by blockade of Ca2+ entry pathways. Constriction induced by ROS thus shows some similarities to HPV. Whilst only providing circumstantial evidence that a rise in ROS might underlie HPV, these results predicate against the concept of a fall in ROS generation being the primary initiator of HPV. Funded by the British Heart Foundation