Analysis of plasma serotonin levels and hemodynamic responses following chronic serotonin infusion in broilers challenged with bacterial lipopolysaccharide and microparticles

There has been extensive interest in the role of serotonin (5-hydoxytryptamine, 5-HT) in the pathogenesis of pulmonary hypertension because episodes of pulmonary arterial hypertension in humans have been linked to serotoninergic appetite-suppressant drugs. In this study, we investigated the role of serotonin in the development of pulmonary hypertension induced by intravenously injecting bacterial lipopolysaccharide (LPS, endotoxin) and cellulose microparticles. In experiment 1, we used a 5-HT ELISA kit for the in vitro quantitative determination of 5-HT in plasma during the development of pulmonary hypertension induced by injecting LPS and cellulose microparticles i.v. in broilers. In experiment 2, broilers were either chronically infused with 5-HT via surgically implanted osmotic pumps or received sham surgery as a control. After a period of 10 d, the pulmonary arterial pressure was recorded during challenge with injected LPS or microparticles. Microparticles elicited 5-HT plasma levels more than 2-fold greater than those elicited by LPS from 15 to 45 min postinjection. This indicates that 5-HT is an important mediator in the pulmonary hypertensive response of broilers to microparticles, but may not play a prominent role in the pulmonary hypertensive response to LPS. Furthermore, chronic 5-HT infusion via osmotic pumps caused an increase in the duration of the pulmonary hypertensive response of broilers to microparticles, indicating that the infused 5-HT was sequestered by circulating thrombocytes and then released upon microparticle-mediated thrombocyte activation. Serotonin appears to play a less prominent role in the pulmonary hypertensive response of broilers to LPS, indicating that other mediators within the innate response to inflammatory stimuli may also be involved. These results are consistent with our hypothesis that pulmonary arterial hypertension ensues when vasoconstrictors such as 5-HT overwhelm the dilatory affects of vasodilators such as nitric oxide, thereby effectively reducing the pulmonary vascular capacity of pulmonary arterial hypertension-susceptible broilers.