Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Experimental Investigation
Repeated Thermal Therapy Up-Regulates Endothelial Nitric Oxide Synthase and Augments Angiogenesis in a Mouse Model of Hindlimb Ischemia
Yuichi AkasakiMasaaki MiyataHideyuki EtoTakahiro ShirasawaNarisato HamadaYoshiyuki IkedaSadatoshi BiroYutaka OtsujiChuwa Tei
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2006 Volume 70 Issue 4 Pages 463-470


Background Nitric oxide (NO), constitutively produced by endothelial NO synthase (eNOS), plays roles in angiogenesis. Having reported that thermal therapy up-regulated the expression of arterial eNOS in hamsters, we investigated whether this therapy increased angiogenesis in mice with hindlimb ischemia. Methods and Results Unilateral hindlimb ischemia was induced in apolipoprotein E-deficient mice, which were divided into control and thermal therapy groups. The latter mice were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 5 weeks. Laser Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls (0.79±0.04 vs 0.54±0.08, p<0.001). Significantly greater capillary density was seen in thermal therapy group (757±123 /mm2 vs 416±20 /mm2, p<0.01). Western blotting showed thermal therapy markedly increased hindlimb eNOS expression. To study possible involvement of eNOS in thermally induced angiogenesis, thermal therapy was given to mice with hindlimb ischemia with or without NG-nitro-L-arginine methyl ester (L-NAME) administration for 5 weeks. L-NAME treatment eliminated angiogenesis induced using thermal therapy. Thermal therapy did not increase angiogenesis in eNOS-deficient mice. Conclusion Angiogenesis was induced via eNOS using thermal therapy in mice with hindlimb ischemia. (Circ J 2006; 70: 463 - 470)

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