Prostaglandin control of plasma and platelet 5-hydroxytryptamine in normal and embolized animals
Utsunomiya, T.; Krausz, M.M.; Shepro, D.; Hechtman, H.B.
American Journal of Physiology 241(5): H766-H771
1981
ISSN/ISBN: 0002-9513 PMID: 7030086 Document Number: 172500
Several abnormalities in cardiopulmonary function following embolization are thought to be mediated by 5-hydroxytryptamine (5-HT). The proven effectiveness of therapy with prostacyclin (PGI2) led to this study of the changes in 5-HT concentrations in plasma and platelets with and without prostaglandin (PG) treatment. Thirty min after introduction of autologous clot 0.5 g/kg in 19 dogs, plasma 5-HT concentrations rose 3-fold (P < 0.001) concomitant with a 29% fall in platelet count. A significant correlation (r = 0.60, P < 0.001) was determined for the observed increase in plasma 5-HT and fall of platelets. Not all 5-HT contained in the lost platelets was released into or remained within plasma, because whole blood 5-HT levels declined (P < 0.05). Platelet 5-HT concentrations were unchanged throughout the 4 h observation period. Infusion of PGI2 (100 ng .cntdot. kg-1 per min) for 1 h caused a decrease in 5-HT concentration in mixed venous plasma (P < 0.005) and an increase of platelet 5-HT (P < 0.001). Similar effects were observed with a PGE1 infusion (400 ng .cntdot. kg-1 per min) for 1 h. Platelet 5-HT concentrations remained elevated 2 h after cessation of PGI2 or PEG1. In 6 normal dogs PGI2 infusion produced similar results. Plasma 5-HT fell (P < 0.01), whereas platelet levels rose (P < 0.025), and clearance of 5-HT by the pulmonary vasculature was inhibited (P < 0.05). After embolization, concentrations of 5-HT in mixed venous blood were related to increases in pulmonary vascular resistance (PVR) (r = 0.76, P < 0.001), but were poorly correlated with physiological dead space (VD/VT) and were not correlated with physiological shunting (.ovrhdot.Qs/.ovrhdot.Qt). Pretreatment with the 5-HT antagonist cyproheptadine (0.5 mg/kg) prevented the rise in PVR but not in VD/VT or .ovrhdot.Qs/.ovrhdot.Qt. 5-HT apparently is of secondary importance in mediating the abnormalities of respiratory gas exchange after embolism. Exogenous PG infusions and perhaps endogenous PG release during embolization inhibit endothelial cell uptake of 5-HT. High PGI2 levels enhance platelet uptake, resulting in elevated platelet and low plasma concentrations of this amine.