Influence of embolism and imipramine on kinetics of serotonin uptake by dog lung.
We previously presented a model from which the kinetic parameters Km and Vmax for serotonin uptake by the lung can be obtained from multiple indicator-dilution data. The purpose of the present study was to determine whether experimentally induced changes in lung endothelial function would be revealed in the kinetic parameters calculated using the model. In experiments using isolated dog lung lobes, embolization with 550-microns glass beads was used to reduce the vascular volume and perfused surface area. Imipramine was used to inhibit the serotonin uptake mechanism. In addition, we studied the influence of the vasodilator papaverine, which in previous studies had been used to block the serotonin-induced vasoconstriction. Embolization, imipramine, and papaverine all significantly reduced percentage uptake of serotonin. The kinetic analysis revealed a significant decrease in the maximum serotonin uptake rate (Vmax) with all three experimental manipulations. In addition, imipramine significantly increased Km. The results indicate that the kinetic parameters obtained from the model do respond to transport inhibition and changes in endothelial surface area, further supporting their usefulness as indexes of endothelial function.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D010208:Papaverine / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011655:Pulmonary Embolism / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects
D012701:Serotonin; D010208:Papaverine; D007099:Imipramine