Mechanism of the Serotonin Effect on Lung Transvascular Fluid and Protein Movement in Awake Sheep

To see how serotonin affects filtration from lung vessels, we measured vascular pressures, lung lymph flow, lung lymph and blood plasma protein concentrations, arterial blood gases, cardiac output, and lung water content in unanesthetized sheep before and during intravenous serotonin infusions and compared serotonin effects with the effects of inflating a balloon in the left atrium in the same sheep. Serotonin caused a dose-related increase in lung lymph flow and a dose-related decrease in lymph-plasma protein concentration ratios. Steady-state 4-hour serotonin infusions at 4 μ/kg min−1 caused lymph flow to increase from 5.4 ± 0.7 (SE) ml/hour to 8.3 ± 1.3 ml/hour, lymph-plasma albumin ratios to fall from 0.78 ± 0.05 to 0.72 ± 0.04, lymph-plasma globulin ratios to fall from 0.64 ± 0.02 to 0.56 ± 0.02, and pulmonary arterial and left atrial pressures to increase by 3 cm H2O each. Lymph clearance and permeability-surface area products for eight protein fractions ranging from 36 A to 96 A in molecular radius during steady-state serotonin infusion studies were not significantly different from those during steady-state increased pressure studies. Four-hour infusions of serotonin at 4/ig/kg min−1 caused a moderate fall in arterial Po2 and a slight increase in arterial pH but did not affect cardiac output or cause pulmonary edema. We conclude that serotonin increases lung transvascular filtration primarily by increasing the transmural pressure gradient in exchanging vessels rather than by increasing vascular permeability.