Vascular reactivity in sepsis: importance of controls and role of nitric oxide.
We have previously reported differential impairment of pulmonary and systemic vascular contractility in hyperdynamic sepsis. The objectives of this study were (1) to determine whether the magnitude of this phenomenon depends on the control group chosen for comparison, and (2) to examine the role of nitric oxide (NO) in this altered vascular contractility. Rats were randomized to sepsis induced by cecal ligation and perforation (CLP) or to one of two control procedures. The Sepsis group had a jugular venous line for fluid administration, laparotomy, and CLP. Control group 1 (Control) had only a jugular venous line inserted, while group 2 (Sham) had a jugular venous line inserted and an abdominal incision. All rats were killed 24 h after surgery. Vascular contractility of small pulmonary arterial and thoracic aortic rings was assessed in vitro by obtaining cumulative dose-response curves to the contractile agonists potassium chloride (KCl), phenylephrine (PE), and prostaglandin F2 alpha (PGF2 alpha). Pulmonary vessels from animals in the Sepsis and Sham groups exhibited significant attenuation of the contractile responses to KCl, PE, and PGF2 alpha compared with the Control group. In contrast, contractility of the aortic rings to KCl, PE, and PGF2 alpha was not significantly different in the three groups studied. Incubation of pulmonary and aortic vessels with NG-nitro-L-argine methyl ester (L-NAME, 10 microM) caused an increase in the response to KCl, PE, and PGF2 alpha in pulmonary vessels in Sepsis and Sham rats but not in Control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Yaghi
A
A
A.C. Burton Vascular Biology Laboratory, Department of Medicine, Victoria Hospital, London, Ontario, Canada.
Paterson
N A
NA
McCormack
D G
DG
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002405:Catheterization, Central Venous; D002432:Cecum / Q000293:injuries; D007416:Intestinal Perforation / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester