Histamine as a factor in tolerance to levarterenol

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Abstract
Tolerance to levarterenol was developed in 18 dogs. It was observed that at the end of 3 hr the mean dose received by these animals was 13.3 µ/kg/min; initially, only a dose of 1–2 µ/kg/min was necessary to maintain an induced arterial pressure of 30–40 mm Hg above the normal. Using the fluorometric assay devised by Shore, the blood level of histamine was found to increase from an initial level of 47.8 ± 5.9 (se) µ/liter to a concentration of 89.6 ± 7.5 (se) µ/liter at the end of the 3-hr infusion of levarterenol. Levarterenol tolerance was also developed in animals whose histamine content had been previously depleted by 48/80. These dogs required an initial average dose of 3.97 µ/kg/min and a final average dose of 6.26 µ/kg/min. In another series of investigations, levarterenol was administered simultaneously with 48/80, and it was found that the dose of levarterenol was directly related to the blood level of histamine. The evidence indicates that levarterenol release histamine and that this release histamine exerts an influence on tolerance development to this pressor amine.