Leukocytes extravasation in acute homocysteinemic rats

Homocysteine may promote atherogenesis and thrombogenesis by enhancing leukocyte–endothelium interactions. We explored this hypothesis in an acute hyperhomocysteinemia rat model, which was created by a continuous venous homocysteine infusion (4 ml/h/kg body weight) with 2.5 and 10 mg/ml , -homocysteine upto 90 min. Venous homocysteine levels were monitored periodically and varied 65–276 μmol/l, a range observed frequently in homocysteinemic and homocystinuric patients. We measured hemodynamic parameters in mesentery by intravital microscopy in rats infused with homocysteine (N=5 for each dose) and saline (N=7). Homocysteine infusion for 90 min did not change the mean carotid arterial blood pressure, velocity of red blood cells and rolling leukocyte flux. However at the dose of 10 mg/ml the venular wall shear rate was reduced to 66–69% of the pre-infusion value (P<0.05). The leukocyte rolling velocity decreased to 78–82% (P<0.05). The number of leukocytes adhering to the venular wall increased 2.4-fold (P<0.05), and the leukocyte extravasation increased 4.7-fold (P<0.001). Each of these effects was time-dependent and homocysteine dose-dependent. But none were observed in saline infused rats. In conclusion, while homocysteine infusion did not change hemodynamic parameters, it significantly enhanced dose-dependent leukocyte–endothelium interactions, which may contribute to homocysteine induced endothelial dysfunction.