title: Leukocytes extravasation in acute homocysteinemic rats.
abstract: 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 micromol/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.
authors.affiliation: Department of Medicine, Prince Henry/Prince of Wales Hospital and Center for Thrombosis and Vascular Biology, University of New South Wales, Sydney, Australia.
authors.forename: Wei Yu
authors.initials: WY
authors.lastname: Fu
authors.forename: Nicholas P B
authors.initials: NP
authors.lastname: Dudman
authors.forename: Michael A
authors.initials: MA
authors.lastname: Perry
authors.forename: Xing Li
authors.initials: XL
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000818:Animals; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000166:cytology; D006439:Hemodynamics; D006710:Homocysteine / Q000097:blood*; D020138:Hyperhomocysteinemia / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006710:Homocysteine