Maintenance of tone, role of arachidonate metabolites, and effects of sensitization in guinea pig trachea

Abstract

A study was made of the mechanisms underlying production of resting active tension in guinea pig tracheal smooth muscle and the changes with active sensitization to ovalbumin. The same types of tissues were also analyzed as to their responses to arachidonate. Responses for each tissue were expressed in relation to a scale between zero active tension and maximum active tension in response to carbachol. A variety of selective and nonselective inhibitors of cyclooxygenase or 5-lipoxygenase were shown to affect active tension in a manner consistent with the conclusion that a cyclooxygenase product, probably prostaglandin F(PGF_2α) and not thromboxanes was chiefly responsible. The inhibition of active tension produced by cyclooxygenase inhibition was shown to be related to the initial active tension, such that tissues with greater resting active tension had greater reductions in tone. No differences of major importance were found as to the mechanisms underlying tone production in control and sensitized tissues. The tension changes in response to exogenous arachidonate were also found to be dependent on the initial level of active tension; when this was low, tension increased, when it was high, tension decreased or did not change. Effects of inhibitors on these responses were again consistent with the conclusion that primarily excitant prostaglandins, not thromboxanes, were produced. Some suggestive evidence for production of excitatory and inhibitory nonprostaglandin metabolites was obtained. No difference of major importance between control and sensitized tissues was observed in the magnitude or underlying mechanism of production of active tension.