Our in vivo results are consistent with the in vitro findings of Ishii and Kato10 who observed suppression of histamine-induced contraction of guinea pig ileum by prior exposure of the tissues to methacholine. They also observed that the suppressive action of methacholine on subsequent histamine-induced contraction was specific, as neither methacholine nor histamine exposure had any effect on subsequent contractile response to methacholine. Furthermore, prior histamine exposure, per se, failed to alter the subsequent contractile response to histamine. Thus, our in vivo findings in normal human airways further extend and confirm the in vitro findings of Ishii and Kato.
Our results are different from a recently reported study by Manning and O’Byrne9 in human subjects with bronchial asthma. Since they did not study normal subjects, we are able to compare the results of our asthmatic group only to those of Manning and O’Byrne. In our asthmatic subjects, prior inhalation of histamine or methacholine caused no suppression of subsequent bronchoconstrictor responses to either agonist. In contrast, Manning and O’Byrne observed a suppression of bronchoconstrictor responses to histamine and acetylcholine by prior inhalation of histamine, and not by prior inhalation of acetylcholine. The reason for these differences is not clear. These differences may be related to variance in the study population, or use of methacholine vs acetylcholine in our study. Although five normal and three asthmatic subjects showed mild tachyphylaxis to histamine, for each group there was no significant tachyphylaxis to histamine. Absence of significant histamine tachyphylaxis in our study may also be related to the fact that airway responses were evaluated by measurements of SGaw and not FEVx. Since histamine tachyphylaxis is a concentration-dependent event,16 it is possible that concentration of inhaled histamine required to change SGaw is different from that needed to change the FEVj, and not enough to produce significant tachyphylaxis. It is also possible that histamine tachyphylaxis may only be exhibited in changes of FEVj and not SGaw. However, these variances in methodology do not explain the differences between normal and asthmatic subjects observed in our study.
Tags: Asthma, Methacholine, muscarinic receptor