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Background In vitro studies have shown that isoflurane, enflurane, and halothane inhibit the hypoxic pulmonary vasoconstriction (HPV) with essentially the same potency. The aim of this study is to compare the effects of sevoflurane and isoflurane on HPV in constant-flow perfused rabbit lungs. Methods Constant-flow perfused lungs from Japanese white rabbits were tested. The lungs were divided into three groups: isoflurane alone (n = 6), sevoflurane alone (n = 6), and sevoflurane with ibuprofen pretreatment (n = 6). Baseline HPV responses were measured as the pulmonary arterial pressure increased after changing inspired oxygen concentration from 95% for 15 min to 3% (with 5% CO2) for 5 min without anesthetic administration. Next, three different concentrations of anesthetics were added to the inspired gas for 15 min in random order. The HPV response in the presence of anesthetic was expressed as a percentage of the pressor response in the absence of anesthetics, and dose-response relationships were calculated using the nonlinear least-squares method. Results Isoflurane and sevoflurane both depressed the HPV response in a dose-related manner. The half-inhibition values (ED50) of HPV with isoflurane and sevoflurane were 0.85 +/- 0.22 MAC and 1.00 +/- 0.12 MAC (mean +/- SD), respectively, and were not statistically different. Ibuprofen pretreatment did not alter ED50 and slope of dose-response curve, although the absolute value of pressor response in the sevoflurane group with ibuprofen pretreatment was greater than that in the sevoflurane alone group at every concentration of sevoflurane. Conclusions Sevoflurane inhibits the HPV response in a dose-related manner, and its potency is similar to that of isoflurane in vitro. Cyclooxygenase products do not mediate the inhibition of HPV by sevoflurane.