The effects of cilostazol on tissue oxygenation upon an ischemic-reperfusion injury in the mouse cerebrum.
Although cilostazol, an inhibitor of cyclic nucleotide phosphodiesterase 3 (PDE3), is known to exert a potent antiplatelet function by raising intracellular cAMP concentration, its effect on cerebral microcirculation upon an ischemic insult is not clearly understood. To examine effects of cilostazol on the global ischemic injury in the brain, we first measured the plasma leakage using modified Miles assay after mice had been subjected to 60 min of a bilateral common carotid artery (BCCA) occlusion followed by reperfusion for 4 h. Oral treatment with cilostazol (30 mg/kg) significantly increased plasma leakage. This result led us to examine if the treatment with cilostazol recruits more capillaries leading to an increase in surface area for exchange and oxygen transport to tissues. To do so, we simultaneously measured degrees of tissue hypoxia and vessel perfusion. Pimonidazol was injected intraperitoneally 1 h before sacrifice and capillary patency was assessed by fluorescein isothiocyanate-labeled Lycopersicon esculentum lectin bound to the endothelial surface. Treatment with cilostazol markedly increased the capillary patency which was accompanied by a reduction in the hypoxic area. Although the treatment with cilostazol caused an increase in the flux of plasma proteins across endothelial barrier that may imply an adverse role after a BCCA occlusion, this increase in protein leakage was attributable to the increased surface area for exchange which in turn brought about a reduction in tissue hypoxia. Taken together cilostazol appears to produce a protective effect against the ischemic-reperfusion injury.
Morikawa
Takayuki
T
Department of Biochemistry and Integrative Medical Biology, Keio University School of Medicine, Tokyo 160-8582, Japan. mi081031@sc.itc.keio.ac.jp
Hattori
Katsuji
K
Kajimura
Mayumi
M
Suematsu
Makoto
M
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology; D054022:Cerebrum / Q000187:drug effects* / Q000473:pathology*; D000077407:Cilostazol; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology*; D014654:Vascular Patency / Q000187:drug effects
D013777:Tetrazoles; D000077407:Cilostazol; D010100:Oxygen