13-Hydroxy-linoleic acid induces airway hyperresponsiveness to histamine and methacholine in guinea pigs in vivo.
The influence of 13-hydroxy-linoleic acid (13-HODE) on the pulmonary resistance and dynamic compliance of guinea pigs in vivo was determined. Intravenously administered histamine and methacholine caused dose-dependent increases in pulmonary resistance and dose-dependent decreases in dynamic compliance in anesthetized, spontaneously breathing guinea pigs. Inhalation of an aerosol containing 13-HODE (10 mumol/L) enhanced the increases in pulmonary resistance observed after administration of histamine or methacholine when compared with the respective control animals. The effect of 13-HODE on the increase in pulmonary resistance after administration of histamine was dose-dependent. An enhancement in the pulmonary resistance was already measured after treatment of guinea pigs with aerosols of solutions containing 0.1 mumol/L 13-HODE when compared with that of control animals. In contrast, the changes in dynamic compliance were not affected by 13-HODE. These results indicate that 13-HODE may play an important role in the induction of airway hyperresponsiveness in vivo when it is produced or released in significant amounts in the airways.
Henricks
P A
PA
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Engels
F
F
van der Linde
H J
HJ
Garssen
J
J
Nijkamp
F P
FP
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D006168:Guinea Pigs; D006632:Histamine / Q000276:immunology*; D008041:Linoleic Acids / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000276:immunology* / Q000503:physiopathology
D008041:Linoleic Acids; D016210:Methacholine Chloride; C042835:13-hydroxylinoleic acid; D006632:Histamine