Vagal stimulation augments pulmonary anaphylaxis in the guinea pig lung.
The effect of bilateral vagal stimulation on aerosolized antigen-induced responses was examined in the sensitized, perfused guinea pig lung. Vagal stimulation in the sensitized, perfused lung resulted in bronchoconstriction (peak response 160 +/- 18% above baseline) that was unaffected by either atropine (1 microM), a muscarinic receptor antagonist, or CP 96,345 (1 microM), a NK-1 receptor antagonist, but was transiently augmented in the presence of physostigmine (1 microM), a cholinesterase inhibitor, through an atropine-sensitive mechanism. However, SR 48968 (1 microM), a NK-2 receptor antagonist, and SR 48968 + CP 96,345 reduced by approximately 50 and 90%, respectively, vagally mediated increases in intratracheal pressure in the perfused lung. Simultaneous challenge with vagal stimulation and aerosolized antigen in the sensitized perfused lung resulted in a significant (p < 0.01) increase in intratracheal pressure (Pi), pulmonary arterial pressure (Ppa), and lung weight (LW) compared with either vagal stimulation or aerosolized antigen alone. Increases in Pi, Ppa, and LW in response to vagal stimulation + aerosolized antigen were associated with elevated venous effluent concentrations of thromboxane A2 (TXA2), prostacyclin, leukotriene C4, and histamine. Vagally mediated potentiation of aerosolized antigen-induced increases in Pi, Ppa, and LW was unaffected by atropine or CP 96,345 but was inhibited by the NK-2 receptor antagonist, SR 48968. These data suggest that vagally mediated (predominantly NK-2) potentiation of aerosolized antigen-induced increases in Pi, Ppa, and LW is characterized by elevated venous effluent concentrations of eicosanoids and histamine.
Tocker
J E
JE
Bronchopulmonary Research, Hoffman-LaRoche, Nutley, New Jersey.
Gertner
S B
SB
Welton
A F
AF
Selig
W M
WM
D000707:Anaphylaxis / Q000503:physiopathology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D009929:Organ Size; D010830:Physostigmine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D014132:Trachea / Q000503:physiopathology; D014630:Vagus Nerve / Q000502:physiology*; D014661:Vasoconstriction / Q000276:immunology / Q000502:physiology
D001549:Benzamides; D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D010880:Piperidines; C073839:SR 48968; D001285:Atropine; D015288:Neurokinin A; D010830:Physostigmine; C066892:CP 96345