Hydrogen peroxide contracts airway smooth muscle: A possible endogenous mechanism

Both distal (canine lung strips) and proximal (bovine trachealis strips) airway smooth muscle contract in isolated organ baths as the percentage of environmental oxygen is increased from 12% to 95%. This effect is blocked by prostaglandin synthetase inhibitors (indomethacin, 102^-4M; meclofenamate, 10^-4M). To determine whether this contractile response is due to molecular oxygen, or to other products of oxidative metabolism, we examined the effects of ozone, hydrogen peroxide, and superoxide radical generating systems (paraquat and xanthine-xanthine oxidase) on the smooth muscle preparations. Ozone (3 ppm), paraquat (2 mM), and xanthine (10^-3M)-xanthine oxidase (1 unit) were without effect. Hydrogen peroxide (10^-5-10^-3M) produced consistent contractions in both preparations, an effect which was appreciably greater in an hypoxic environment and which was blocked by both indomethacin and meclofenamate. Contraction from both hyperoxia and hydrogen peroxide was partially reversed by various oxygen radical scavengers, including methional (10 mM), ascorbic acid (10 mM), nitroblue tetrazolium (0.3 mM), butylated hydroxyanisole (1 mM), and 2′,7′ naphthalonediol (1 nM). These results suggest that hyperoxic contraction in airway smooth muscle is mediated by active oxygen species, perhaps by thier effects on prostaglandin metabolism.