Fibrinogen and fragment D-induced vascular constriction

Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1257-64. doi: 10.1152/ajpheart.00856.2004.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aorta / drug effects*
  • Aorta / physiology
  • Arterioles / drug effects
  • Arterioles / physiology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Femoral Artery / drug effects*
  • Femoral Artery / physiology
  • Fibrin Fibrinogen Degradation Products / pharmacology*
  • Fibrinogen / pharmacology*
  • In Vitro Techniques
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Muscle, Skeletal / blood supply
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Vasoconstriction / drug effects*

Substances

  • Fibrin Fibrinogen Degradation Products
  • fibrinogen D fragment
  • Intercellular Adhesion Molecule-1
  • Fibrinogen