1. Small arteries were isolated from either rat mesentery or human subcutaneous fat, and mounted in a myograph for the measurement of isometric force.
2. Superoxide dismutase, either in the presence or absence of catalase, relaxed noradrenaline-induced tone. This effect was abolished by removal of the endothelium or incubation with an inhibitor of NO synthase, N-ω-nitro-L-arginine methyl ester. Catalase alone had a negligible effect on noradrenaline-induced tone.
3. Captopril, an angiotensin-converting enzyme inhibitor and putative free-radical scavenger, did not relax pre-contracted isolated vessels. N-Acetylcysteine caused an endothelium-independent relaxation of rat vessels. Similar effects were observed in human vessels.
4. Acetylcholine induced a concentration-dependent relaxation of isolated resistance arteries, which was inhibited by removal of the endothelium or N-ω-nitro-L-arginine methyl ester, but unaffected by indomethacin. Preincubation with captopril, N-acetylcysteine or catalase alone did not alter the acetylcholine concentration-response relationship, but superoxide dismutase in combination with catalase enhanced responses to acetylcholine, causing a six-fold increase in potency.
5. Superoxide dismutase causes endothelium-dependent relaxation of resistance arteries and potentiates responses to acetylcholine. This action is probably due to the ability of the enzyme to scavenge superoxide anions which inhibit endothelium-dependent relaxation.
6. N-Acetylcysteine causes an endothelium-independent relaxation of resistance arteries which is probably unrelated to the putative ability of this compound to scavenge superoxide radicals and may reflect a direct action on vascular smooth muscle.