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.
Park
K W
KW
Department of Anesthesia & Critical Care, Beth Israel Hospital, Harvard Medical School, Boston, MA 02215, USA.
Dai
H B
HB
Lowenstein
E
E
Darvish
A
A
Sellke
F W
FW
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D005609:Free Radicals / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008353:Mannitol / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D005609:Free Radicals; D007093:Imidazoles; C039242:dazmegrel; D008353:Mannitol; D007530:Isoflurane; D013482:Superoxide Dismutase; D013930:Thromboxane-A Synthase; D010100:Oxygen