Purpose: The volatile anaesthetics enflurane and isoflurane inhibit the endothelium dependent-relaxation in some in vitro preparations. To determine their site of action on the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) pathway, experiments were conducted in a bioassay system.
Method: Continuously perfused cultured bovine aortic endothelial cells (BAEC) were the source of EDRF/NO while a phenylephrine-precontracted denuded rabbit aortic ring, directly superfused by the BAEC effluent served to detect EDRF/NO. The effect of basal and bradykinin (Bk)-stimulated EDRF/NO release on vascular tension was measured. The effect of 4% enflurane or 2% isoflurane on EDRF/NO-induced relaxation was determined.
Results: Enflurane added to the perfusate either upstream or downstream in relation to BAEC attenuated the relaxation induced by Bk at low concentrations. On the other hand, isoflurane, added either upstream or down-stream to BAEC, potentiated the relaxation induced by the basal release of EDRF but attenuated the relaxation induced by the Bk stimulated release of EDRF. Neither enflurane nor isoflurane attenuated the relaxation induced by sodium nitroprusside (SNP), an NO donor.
Conclusion: Enflurane decreases the stability of EDRF/NO released after Bk stimulation while isoflurane can have opposite effects depending on whether the relaxation results from basal or Bk-stimulated release of endothelial derived relaxing factor(s). Isoflurane increases the stability or action of the basal relaxing factor, decreases the stability of the Bk-stimulated relaxing factor (which is probably NO).