Pitavastatin attenuates leukocyte-endothelial interactions induced by ischemia-reperfusion injury in the rat retina.
OBJECTIVE
Statins (3-hydroxy-methylglutaryl coenzyme A reductase inhibitors) have been shown to lower serum cholesterol levels in clinical use. Moreover, it has been reported that statins exert pleiotropic and beneficial effects on vascular endothelium. Therefore, we investigated the effects of pitavastatin, a new statin, on leukocyte accumulation during ischemia-reperfusion injury.


METHODS
Transient retinal ischemia was induced in Long-Evans rats for 60 min by temporal ligation of the optic nerve. Pitavastatin (0.12, 0.35, or 1.1 mg/kg) was administered 5 min prior to the induction of retinal ischemia. Leukocyte-endothelial interactions in the post-ischemic retina were evaluated in vivo with acridine orange digital fluorography. The number of rolling leukocytes, number of accumulated leukocytes, and diameters of the major retinal artery and vein were evaluated. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression in the retina was semiquantitatively studied using the RT-PCR method.


RESULTS
Pitavastatin-treated rats at doses of 0.35 and 1.1 mg/kg showed mild arterial narrowing (p < 0.01) and venous dilation (p < 0.01) compared with vehicle-treated (ischemic) rats. In rats treated with 0.35 mg/kg pitavastatin, the number of rolling leukocytes was significantly reduced by 35.5% (p < 0.01) 12 hr after reperfusion compared with that of vehicle-treated rats. With treatment at a dose of 0.35 mg/kg pitavastatin, the number of accumulated leukocytes was reduced to 68.7% (p < 0.01) 24 hr after reperfusion. Moreover, pitavastatin treatment significantly reduced ICAM-1 mRNA expression in the retina during ischemia-reperfusion injury.


CONCLUSIONS
Pitavastatin effectively attenuated ischemia-induced leukocyte-endothelial interactions in the rat retina.
Miyaki
Kenichi
K
Department of Ophthalmology and Visual Sciences, Nagoya City University Graduate School of Medicine, Mizuho-ku, Nagoya, Japan.
Matsubara
Akihisa
A
Nishiwaki
Akiko
A
Tomida
Kazuyuki
K
Morita
Hiroshi
H
Yoshida
Munenori
M
Ogura
Yuichiro
Y
D000165:Acridine Orange / Q000378:metabolism; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D012164:Retinal Diseases / Q000378:metabolism / Q000503:physiopathology*; D012171:Retinal Vessels / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D000165:Acridine Orange; C108475:pitavastatin