title: Attenuation of vascular endothelial dysfunction by testosterone receptor blockade after trauma and hemorrhagic shock.
abstract: OBJECTIVE
  The salutary effects of the testosterone receptor antagonist flutamide on the depressed immune and cardiovascular functions after hemorrhage and resuscitation are related to improved endothelial cell function, which can subsequently lead to an increase in organ blood flow, oxygen delivery, and tissue oxygen consumption.
  
  
  METHODS
  Male adult rats underwent a 5-cm midline laparotomy (ie, trauma) and were bled to and maintained at a mean systemic arterial pressure of 40 mm Hg until 40% maximal blood-out volume was returned in the form of Ringer lactate). The animals were then resuscitated with 4 times the total volume of shed blood with Ringer lactate for 60 minutes. Flutamide (25 mg/kg) or an equivalent volume of the vehicle propanediol was injected subcutaneously 15 minutes before the end of resuscitation. At 20 hours after resuscitation, aortic rings (approximately 2.5 mm in length) were isolated and mounted in an organ chamber. Dose responses for an endothelium-dependent vasodilator (acetylcholine chloride) and endothelium-independent vasodilator (nitroglycerine) were determined. Organ blood flow was measured using strontium 85-labeled microspheres. Total hemoglobin and oxygen content in the femoral artery and portal, hepatic, and renal veins were determined. Oxygen delivery and consumption in liver, small intestine, and kidneys were calculated.
  
  
  RESULTS
  Administration of flutamide after trauma-hemorrhage attenuated the depressed endothelial function. Furthermore, flutamide treatment restored the reduced blood flow and oxygen delivery and consumption in all organs tested after trauma-hemorrhage and resuscitation.
  
  
  CONCLUSIONS
  Flutamide appears to be a useful adjunct for improving vascular endothelial function and regional hemodynamics after trauma-hemorrhage and resuscitation.
authors.affiliation: Center for Surgical Research, University of Alabama at Birmingham, 1670 University Blvd, Volker Hall, Room G094, Birmingham, AL 35294-0019, USA. Irshad.Chaudry@ccc.uab.edu
authors.forename: Z F
authors.initials: ZF
authors.lastname: Ba
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: D J
authors.initials: DJ
authors.lastname: Koo
authors.forename: D A
authors.initials: DA
authors.lastname: Ornan
authors.forename: K I
authors.initials: KI
authors.lastname: Bland
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000818:Animals; D001011:Aorta / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005485:Flutamide / Q000494:pharmacology; D006454:Hemoglobins / Q000032:analysis; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D014665:Vasodilator Agents / Q000494:pharmacology; D014947:Wounds and Injuries / Q000150:complications*
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D006454:Hemoglobins; D011944:Receptors, Androgen; D014665:Vasodilator Agents; D005485:Flutamide; D005996:Nitroglycerin; D000109:Acetylcholine