Effects of histamine, 5-hydroxytryptamine and bradykinin on the vascular system of isolated lungs of the guinea-pig and the influence of phenylbutazone on these effects.

1. In isolated lungs of the guinea-pig perfused through the pulmonary artery repeated doses of histamine progressively increased pulmonary arterial pressure and reduced fluctuations in tracheal pressure. Phenylbutazone almost completely abolished the effect of histamine on the arterial pressure and suppressed the progression of the effect on tracheal pressure.2. The effects of 5-hydroxytryptamine and bradykinin did not show such progression.3. The fractions of radioactivity remaining in the lungs after doses of (14)C-histamine did not differ significantly after successive doses. The outflow of radioactivity from previously loaded lungs was greatly increased by histamine, bradykinin and 5-hydroxytryptamine. This increase was not affected by papaverine.4. Successive doses of histamine, but not 5-hydroxytryptamine, produced a progressive increase in weight of the lungs and this effect was accompanied by a progressive increase in arterial pressure. Both effects were strongly suppressed by phenylbutazone.5. It is concluded that repeated administration of histamine causes an accumulation of fluid in the lungs probably mainly in the interstitial spaces, which results in an inhibition of the tracheal pressure fluctuations. Phenylbutazone prevents this effect by suppressing the vasoconstrictor action of histamine without affecting the increased vascular permeability.