Interaction between aspirin and prostaglandins in the isolated guinea-pig tracheal muscle.

Abstract

Abstract-The effects of PGE2 and PGF2a on the tonus of isolated guinea-pig tracheal chain were investigated and compared with those of histamine and acetylcholine.PGE2 reduced tonus in normal resting state, but elevated tracheal tonus reduced by aspirin. Such PGE2-induced contractions did not exceed the initial resting tonus, and the magnitude and duration of the contractions progressively diminished with increase of PGE2 concentrations. Aspirin produced neither relaxation nor contraction in the presence of a low dose of PGE2.Unlike PGE2, PGF2a produced a dose-related contraction in the normal tracheal chain, and the contractile response to PGF2a was markedly potentiated by aspirin.In the presence of PGF2a, aspirin no longer produced tracheal relaxation but produced a dose-related contraction. The contractile effect of histamine but not of acetylcholine was also potentiated by aspirin, but there was a slight difference between PGF2a and histamine in that the potentiation of action of PGF2a by aspirin was more easily diminished by PGE2. These results suggest that PGE2 plays an important role in the maintenance of the resting tonus of the isolated guinea-pig tracheal chain, and in large doses it also acts as a tracheal relaxant and attenuates the tracheal responses to PGF2a and histamine.Aspirin-like drugs have been shown to inhibit prostaglandin (PG) biosynthesis in some 30 different systems (1, 2). Our previous report (3) showed that relatively low doses of aspirin-like drugs reduced dose-dependently the resting tonus of the isolated guinea-pig tracheal chain, and that there was a highly significant correlation between the degree of relaxation of the tracheal chain and the inhibitory effect on the contraction of the isolated rat stomach induced by arachidonic acid, a precursor of PGs. The antagonistic effect of aspirin-like drugs against arachidonic acid was considered to be due to inhibition of PG biosynthesis since the drugs had no direct antagonistic effect against PGs in the rat stomach fundus strips (3). The results suggest that the inhibition of PG biosynthesis may be re sponsible for the relaxation of the isolated guinea-pig tracheal chain.

Effects of Na removal and readmission on the mechanical response in the guinea-pig tracheal smooth muscle.

“…When Na is readmitted, marked relaxation is produced and then the tension slowly returns. Since the muscle tone is abolished by indomethacin (OREHEK et al, 1975), or by aspirin (ONo et al, 1979), prostaglandins are probably involved in the generation of the sustained tension in the normal medium. Thus, it is possible that the decrease in muscle tone in Na-free solution is a result of reduction of prostaglandin synthesis or of the responsiveness to prostaglandins.…”