title: Fibrinogen and fragment D-induced vascular constriction.
abstract: Elevated fibrinogen (Fg) concentration in blood is a high risk factor for many cardiovascular diseases. We hypothesize that Fg and its early degradation product, fragment D, may result in arterial constriction by binding endothelial intercellular adhesion molecule-1 (ICAM-1). The vasoconstriction induced by Fg and fragment D was studied in third- and second-order arterioles (3As and 2As, respectively) of Sprague-Dawley rat cremaster muscle in vivo, in aortic and femoral artery rings, and in the segments of first-order arterioles (1As) isolated from rat cremaster muscle. Intravascular infusion of Fg induced significant constriction of 3As and 2As (by 33.4 +/- 3.4 and 23.7 +/- 4.3%, respectively) in vivo and was abolished in the presence of the specific endothelin type A receptor blocker BQ-610. Fg and fragment D produced significant constriction of both aortic and femoral artery rings. Isolated 1As constricted in response to Fg (0.3 microM) and fragment D (3 microM) by 31 +/- 1.4 and 12 +/- 1.5%, respectively. Fluorescently labeled Fg and fragment D bound to the vascular wall, whereas albumin bound to a significantly lesser degree. The binding of Fg and fragment D to the arteriolar wall and constriction of aortic and femoral artery rings as well as isolated 1As were abolished in the presence of anti-Fg and anti-ICAM-1 antibodies. These results indicate that binding of Fg and fragment D to the vascular wall through ICAM-1 may contribute to the increased vascular tone and resistance that compromise circulation.
authors.affiliation: Department of Physiology and Biophysics, Health Sciences Center, University of Louisville, Kentucky 40292, USA. dglomi01@louisville.edu <dglomi01@louisville.edu>
authors.forename: David
authors.initials: D
authors.lastname: Lominadze
authors.forename: Nina
authors.initials: N
authors.lastname: Tsakadze
authors.forename: Utpal
authors.initials: U
authors.lastname: Sen
authors.forename: Jeff C
authors.initials: JC
authors.lastname: Falcone
authors.forename: Stanley E
authors.initials: SE
authors.lastname: D'Souza
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005340:Fibrinogen / Q000494:pharmacology*; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C015214:fibrinogen D fragment; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen