Oxygen-Derived Free Radicals Mediate Isoflurane-Induced Vasoconstriction of Rabbit Coronary Resistance Arteries

• Published in: Anesthesia and analgesia Vol. 80; no. 6; pp. 1163 - 1167
• Main Authors: Park, Kyung W., Dai, Hai B., Lowenstein, Edward, Darvish, Amir, Sellke, Frank W.
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01.06.1995; Lippincott
• Subjects: Anesthetics. Neuromuscular blocking agents; Animals; Arterioles - drug effects; Arterioles - physiology; Biological and medical sciences; Coronary Vessels - drug effects; Coronary Vessels - physiology; Free Radicals - metabolism; Imidazoles - pharmacology; In Vitro Techniques; Isoflurane - pharmacology; Mannitol - pharmacology; Medical sciences; Neuropharmacology; Oxygen - metabolism; Pharmacology. Drug treatments; Rabbits; Superoxide Dismutase - pharmacology; Thromboxane-A Synthase - antagonists & inhibitors; Vasoconstriction - drug effects; Vasoconstriction - physiology; Volatile compound; Oxygen; Coronary artery; Vasoconstriction; Rabbit; General anesthesia; Lagomorpha; In vitro; Free radical; Vertebrata; Mammalia; General anesthetic; Vascular resistance; Animal; Mechanism of action
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1097/00000539-199506000-00017

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.(Anesth Analg 1995;80:1163-7)