HALOTHANE INHIBITS THE PRESSOR EFFECT OF DIPHENYLENEIODONIUM

1 We have recently found that diphenyleneiodonium (DPI), a novel inhib itor of nitric oxide (NO) synthase, causes pressor and tachycardic res ponses in pentobarbitone- but not halothane-anaesthetized rats. The pr esent study investigated the mechanism by which halothane suppresses t he pressor response of DPI. The effects of halothane on the pressor re sponse of DPI were also compared with those of other anaesthetic agent s. 2 In conscious rats, i.v. bolus injections of DPI (0.025- 1.6 mg kg -1) caused dose-dependent increases in mean arterial pressure (MAP), w ith ED50 of 0.07 +/- 0.01 mg kg-1 and maximal rise of MAP (E(max)) of 59 +/- 2 mmHg. While ketamine potentiated E(max) without altering the ED50 and pentobarbitone increased the ED50 without changing E(max) of the pressor response to DPI, chloralose, urethane and ethanol displace d the curve to the right and potentiated E(max). In contrast, halothan e (0.5-1.25%) dose-dependently and non-competitively reduced the press or responses to DPI. 3 Intravenous bolus injection of a single dose of DPI (1.6 mg kg-1) caused immediate and large increases in plasma nora drenaline and adrenaline, as well as MAP in conscious rats. Halothane (1.25%) almost completely inhibited these increases. 4 The results sug gest that DPI causes a pressor response in conscious rats by activatin g the sympathetic nervous system and halothane abolishes this pressor response by inhibiting activities of the sympathetic nervous system. T he results also show that influences of anaesthetics must be taken int o consideration when evaluating pressor response of vasoactive agents.