Oxygen-derived free radicals mediate isoflurane-induced vasoconstriction of rabbit coronary resistance arteries

Isoflurane induces endothelium-dependent constriction of rabbit coronary resistance arteries in vitro. This effect is inhibited by the cyclooxygenase inhibitor indomethacin. To determine whether thromboxane or oxygen-derived free radicals, a byproduct in the cyclooxygenase pathway, mediate this effect, subepicardial coronary arterioles (103 +/- 21 mu) from New Zealand White rabbits were studied in vitro in a pressurized (40 mm Hg), no-flow state using videomicroscopy. The vessels were subjected to increasing concentrations of isoflurane, 0%-3%, in the presence of Dazmegrel (a specific inhibitor of thromboxane synthesis; Pfizer Ltd., Sandwich, UK) or SOD-Mn (manganese superoxide dismutase, a scavenger of superoxide radicals) or mannitol (hydroxyl radical scavenger) 20 or 100 mM or in their absence (control). The control vessels showed a concentration-dependent constriction to isoflurane (P < 0.0001), with reduction in internal diameter of 11.4% +/- 3.5% at isoflurane 3%. This response was unaffected by Dazmegrel (P = 0.78), but was abolished by SOD-Mn (P < 0.01) or mannitol (P < 0.01). We conclude that isoflurane causes concentration-dependent constriction of rabbit coronary resistance arteries and that this effect is mediated by oxygen-derived free radicals.