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 D,L-homocysteine upto 90 min. Venous homocysteine levels were monitored periodically and varied 65-276 mumol/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 or 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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.