Effect of histamine, acetylcholine and compound 48/80 on bronchoconstriction and release of eicosanoids in the dog

The effects of Hi and ACH aerosol and of intravenous infusion of compound 48/80 on bronchoconstriction and plasma levels of Hi, TXB2, KH2PGF2 alpha and KH2PGE2 were investigated in 11 bastard dogs. Administration of Hi and ACH aerosol induced bronchoconstriction accompanied by an increase in the plasma levels of Hi and TXB2. No effect on the plasma levels of KH2PGF2 alpha and KH2PGE2 was detected. Release of endogenous Hi by compound 48/80 induced bronchoconstriction and significant increases in the plasma levels of TXB2 as well as of KH2PGF2 alpha and KH2PGE2. The effects of a second administration of Hi and ACH aerosols after compound 48/80 did not differ qualitatively from the effects of the first aerosol administration. However, quantitatively, the second Hi aerosol induced significantly less bronchoconstriction and TXB2 release. Similarly, effects of the second ACH aerosol tended to be decreased as compared to the first ACH aerosol, although the difference was not significant. The diminished effect of the agonists could be due to receptor desensibilization and/or release of adrenaline, which in turn decreases bronchoconstriction and eicosanoid release.