Influence of vasoconstriction, temperature, and flow on the kinetics of serotonin uptake in rabbit lungs.
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.
Peeters
F A
FA
Division of Pharmacology, Faculty of Medicine, University of Antwerp (UIA), Wilrijk, Belgium.
Bult
H
H
Rampart
M
M
Corten
I
I
Herman
A G
AG
D000818:Animals; D001693:Biological Transport, Active; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010477:Perfusion; D011652:Pulmonary Circulation; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D013696:Temperature; D014661:Vasoconstriction
D012701:Serotonin