Intestinal reperfusion up-regulates inducible nitric oxide synthase activity within the lung.
BACKGROUND
This study examines the hypothesis that pulmonary inducible nitric oxide synthase (iNOS) activity is up-regulated during intestinal reperfusion and that inhibition of NO generation exacerbates pulmonary microvascular dysfunction.


METHODS
Sprague-Dawley rats underwent intestinal ischemia and reperfusion (IIR) or sham operation (SHAM). Pulmonary iNOS activity was measured by quantitating the conversion of L-arginine (L-Arg) to L-citrulline. Another set of animals undergoing IIR or SHAM received an inhibitor of NOS (NG-nitro-L-arginine methylester; L-NAME; 20 mg/kg intravenously), substrate for NO generation (L-Arg; 300 mg/kg intravenously), or vehicle (normal saline solution; 3 ml). Pulmonary microvascular dysfunction was then quantitated by measuring the extravasation of Evans blue dye (EBD) into the lung.


RESULTS
Inducible NOS activity was six times greater in the lungs of animals sustaining IIR when compared with SHAM (p = 0.0005). The concentration of EBD within the lungs of animals sustaining IIR was 30% greater than SHAM (p < 0.05). Inhibiting NOS with L-NAME significantly increased pulmonary EBD concentration of both IIR and SHAM groups when compared with normal saline solution-treated animals (p < 0.0001). Treatment with L-Arg prevented this IIR-induced increase in pulmonary dye extravasation.


CONCLUSIONS
These data suggest that pulmonary iNOS activity is up-regulated in animals sustaining IIR and that this may serve as a compensatory protective response to remote organ injury.
Turnage
R H
RH
Department of Surgery, University of Texas Southwestern Medical School, Dallas 75235-9031, USA.
Kadesky
K M
KM
Bartula
L
L
Myers
S I
SI
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects; D005070:Evans Blue; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000201:enzymology*; D008168:Lung / Q000201:enzymology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D009569:Nitric Oxide; D005070:Evans Blue; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester