NDLI: Dipyridamole Reverses Peripheral Ischemia and Induces Angiogenesis in the Db/Db Diabetic Mouse Hind Limb Model by Decreasing Oxidative Stress

Content Provider	PubMed Central
Author	Pattillo, Christopher B. Bir, Shyamal C. Branch, Billy G. Greber, Eric Shen, Xinggui Pardue, Sibile Patel, Rakesh P. Kevil, Christopher G.
Copyright Year	2010
Abstract	Dipyridamole anti-platelet therapy has previously been suggested to ameliorate chronic tissue ischemia in healthy animals. However, it is not known if dipyridamole therapy represents a viable approach to alleviating chronic peripheral tissue ischemia associated with type 2 diabetes. Here we examine the hypothesis that dipyridamole treatment restores reperfusion of chronic hind limb ischemia in the murine B6.BKS-Leprdb/db diabetic model. Dipyridamole therapy quickly rectified ischemic hind limb blood flow to near pre-ligation levels within three days after starting therapy. Restoration of ischemic tissue blood flow was associated with increased vascular density and endothelial cell proliferation observed only in ischemic limbs. Dipyridamole significantly increased total nitric oxide metabolite levels (NOx) in tissue that were not associated with changes in eNOS expression or phosphorylation. Interestingly, dipyridamole therapy significantly decreased ischemic tissue superoxide and protein carbonyl levels identifying a dominant antioxidant mechanistic response. Dipyridamole therapy also moderately reduced diabetic hyperglycemia and attenuated development of dyslipidemia over time. Together, these data reveal that dipyridamole therapy is an effective modality for the treatment of chronic tissue ischemia during diabetes and highlights the importance of dipyridamole antioxidant activity in restoring tissue NO bioavailability during diabetes.
Related Links	http://dx.doi.org/10.1016/j.freeradbiomed.2010.10.714
Ending Page	269
Page Count	8
Starting Page	262
File Format	PDF
ISSN	08915849
e-ISSN	18734596
Journal	Free radical biology & medicine
Issue Number	2
Volume Number	50
Language	English
Publisher Date	2011-01-01
Access Restriction	Open
Subject Keyword	Physiology (medical) Biochemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology (medical) Biochemistry

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