Halothane inhibits the pressor effect of diphenyleneiodonium.
1. We have recently found that diphenyleneiodonium (DPI), a novel inhibitor of nitric oxide (NO) synthase, causes pressor and tachycardic responses in pentobarbitone- but not halothane-anaesthetized rats. The present study investigated the mechanism by which halothane suppresses the pressor response of DPI. The effects of halothane on the pressor response of DPI were also compared with those of other anaesthetic agents. 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), with ED90 of 0.07 +/- 0.01 mg kg-1 and maximal rise of MAP (Emax) of 59 +/- 2 mmHg. While ketamine potentiated Emax without altering the ED50 and pentobarbitone increased the ED50 without changing Emax of the pressor response to DPI, chloralose, urethane and ethanol displaced the curve to the right and potentiated Emax. In contrast, halothane (0.5-1.25%) dose-dependently and non-competitively reduced the pressor 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 noradrenaline and adrenaline, as well as MAP in conscious rats. Halothane (1.25%) almost completely inhibited these increases. 4. The results suggest that DPI causes a pressor response in conscious rats by activating the sympathetic nervous system and halothane abolishes this pressor response by inhibiting activities of the sympathetic nervous system. The results also show that influences of anaesthetics must be taken into consideration when evaluating pressor response of vasoactive agents.
Wang
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Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Pang
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D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D066298:In Vitro Techniques; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D009861:Onium Compounds / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000777:Anesthetics; D002395:Catecholamines; D009861:Onium Compounds; C007517:diphenyleneiodonium; D009247:NADH, NADPH Oxidoreductases; D006221:Halothane