Pravastatin attenuates lower torso ischaemia-reperfusion-induced lung injury by upregulating constitutive endothelial nitric oxide synthase.
OBJECTIVE
to elicit whether pre-treatment with pravastatin will prevent or ameliorate the acute lung injury that occurs following lower torso ischaemia-reperfusion (IR) in an experimental animal model.


METHODS
male Sprague-Dawley rats were randomised into three groups (n=7/group). The control group underwent a sham laparotomy and aortic dissection. The second group underwent infrarenal aortic cross clamping for 30 min followed by reperfusion for 120 min. The third group pre-treated with pravastatin sodium (0.4 mg/kg/day over 5 days) were again subjected to an ischaemia-reperfusion (IR) injury. The parameters used to assess lung injury included: Wet to dry lung weight ratio (W:D), myeloperoxidase activity (MPO), protein concentration (BALprot) and neutrophil count (BAL PMN) of bronchoaveolar lavage fluid. Western blotting was used to determine the expression of constitutive endothelial nitric oxide synthase (ecNOS) within lung tissue.


RESULTS
IR causes an acute lung injury as indicated by statistically significant differences in W:D lung weight ratios, MPO activity, neutrophil count and BALprotein concentration in the IR group over that of controls. Pre-treatment with pravastatin attenuated this neutrophil infiltration and microvascular leakage. The pravastatin group showed a marked increased expression of ecNOS over that of the IR group and controls.


CONCLUSIONS
this data indicates that pre-treatment with pravastatin protects against ischaemia-reperfusion induced lung injury in an experimental animal model. We believe that its mechanism of action involves an upregulation of ecNOS, which increases basal expression of nitric oxide providing protective effects on the pulmonary circulation against microvascular injury.
Joyce
M
M
Department of Surgery, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
Kelly
C J
CJ
Chen
G
G
Bouchier-Hayes
D J
DJ
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D015854:Up-Regulation
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D017035:Pravastatin