Selective inhibition of inducible nitric oxide in ischemia-reperfusion of rat small intestine.
OBJECTIVE
We investigated the role of constitutive and inducible nitric oxide (NO) synthases in intestinal ischemia-reperfusion (I/R) injury by observing the alterations in hemodynamics and intestinal microcirculation in response to I/R in rats, with or without inhibitors of NO synthases.


METHODS
Adult male Sprague-Dawley rats (n = 9/group) received a standard I/R procedure alone: I/R plus intravenous administration of aminoguanidine (an inhibitor of inducible NO synthase); I/R plus L-NAME (NG-nitro-L-arginine methyl ester, an inhibitor of constitutive and inducible NO synthase); IR + L-Arg (L-arginine, an NO precursor); or a sham operation plus the vehicle. The I/R procedure was performed by clamping the perfusion vessels of a segment of the terminal ileum, and medication was administered intravenously before and after intestinal ischemia. The intestinal perfusion and leukocyte-endothelial interactions were evaluated with in vivo microscopy and laser Doppler flowmetry. Surface expression of CD11b (an adhesion molecule) of circulating granulocytes was measured with flow cytometry.


RESULTS
Intestinal I/R produced circulatory alterations, intestinal microcirculatory derangement, energy depletion, and lipid peroxidation. Aminoguanidine significantly attenuated the reperfusion-related depression of mean arterial pressure (MAP), the decrease in intestinal perfusion index, the decrease in tissue ATP preservation, the increase in tissue malondialdehyde (MDA) level, and the expression of CD11b of circulating granulocytes. Administration of L-NAME had only minor and transient effects on reperfusion-related changes of MAP, intestinal flux, numbers of adherent leukocytes, and CD11b expression, but had some protective effects on tissue MDA and adenosine triphosphate levels and flow velocity. L-Arg further decreased the MAP but did not affect reperfusion-related variables.


CONCLUSIONS
Our results show that the selective inhibition of inducible NO synthase by aminoguanidine attenuates the hemodynamic and microcirculatory derangement that results from intestinal I/R.
Chen
J C
JC
Department of Emergency Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Chen
H M
HM
Shyr
M H
MH
Fan
L L
LL
Chi
T Y
TY
Chi
C P
CP
Chen
M F
MF
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D018845:CD11 Antigens / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007421:Intestine, Small / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D018845:CD11 Antigens; D004791:Enzyme Inhibitors; D006146:Guanidines; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester