Antol, P. J.

Three consecutive dose-response curves to aerosolized histamine were obtained in 11 anesthetized dogs. All dogs showed desensitization (i.e., tachyphylaxis) to high doses of histamine. Tachyphylaxis was highly reproducible. No tachyphylaxis occurred with inhaled acetylcholine or methacholine. Beta-Adrenergic blockade with propranolol or muscarinic blockade with atropine given intravenously had no effect on the histamine tachyphylaxis. Duration of thiamylal anesthesia did not alter the histamine responsiveness. Histamine tachyphylaxis was also seen with chloralose-urethan anesthesia. Since tachyphylaxis is not observed with acetylcholine, it cannot be attributed to a general decline in muscle contractility. We conclude that histamine tachyphylaxis in vivo is not explained by effects of cholinergic reflexes, catecholamine release, duration of anesthesia, or, probably, type of anesthetic agent.

Tachyphylaxis to aerosolized histamine was studied in dogs anesthetized with thiamylal after pretreatment with prostaglandin synthesis inhibitors. Three consecutive histamine dose-response curves were obtained in nine dogs pretreated with 5 mg/kg indomethacin; two of these nine were also pretreated with 10 mg/kg indomethacin. Seven of the nine dogs were pretreated with 4 mg/kg sodium meclofenamate; four of these seven were also pretreated with 12 mg/kg. All dogs had tachyphylaxis at high concentrations of histamine regardless of inhibitor used. Pretreatment with indomethacin while the dogs were under alpha-chloralose-urethan anesthesia gave similar results. Histamine tachyphylaxis was also studied both in the presence and in the absence of indomethacin in tracheal smooth muscle strips obtained from seven additional dogs. A decrease in the median effective dose to histamine was observed in the indomethacin-treated strips, but tachyphylaxis to histamine remained. We conclude that prostaglandin synthesis inhibition does not reverse histamine tachyphylaxis either in vivo or in vitro. Thus the mechanism of histamine tachyphylaxis remains unexplained.