Journal of Applied Physiology, Vol 70, Issue 6 2703-2711, Copyright © 1991 by American Physiological Society
Influence of vasoconstriction, temperature, and flow on the kinetics of serotonin uptake in rabbit lungs
F. A. Peeters, H. Bult, M. Rampart, I. Corten and A. G. Herman
Division of Pharmacology, Faculty of Medicine, University of Antwerp (UIA), Wilrijk, Belgium.
In the process of estimating the kinetic parameters of the pulmonary
endothelial serotonin (5-HT) uptake, it is critically important to
distinguish the effects of hemodynamic changes from endothelial injury.
Therefore, the effects of changes in flow rate (1.7-5.0 ml/s), hemodynamics
(vasoconstriction by norepinephrine), and temperature (39 vs. 33 degrees C)
were investigated in isolated rabbit lungs. Indicator-dilution data were
expressed in terms of the Michaelis-Menten equation for the two 5-HT uptake
pathways in the preparation. The maximum uptake velocity (Vmax1) and the
5-HT concentration at half-maximum velocity (Km1) of the first pathway as
well as the first-order constant (Vmax2/Km2) of the linear part of the
second pathway were determined. Neither vasoconstriction nor flow
variations had any effect on Km1, whereas increasing the flow rate caused
extensive recruitment, with a concomitant increase in Vmax1 and Vmax2/Km2.
Furthermore, all the kinetic parameters were significantly decreased at the
lower temperature. We conclude that Km1 is independent of organ
hemodynamics (vasoconstriction and flow) but susceptible to changes in 5-HT
uptake capacity caused by a change in temperature. Vmax1 and Vmax2/Km2
respond to alterations in 5-HT uptake capacity and perfused organ volume.
These are prerequisites to apply kinetic modeling as a method for the
investigation of pulmonary endothelial function and integrity.
