Dipyridamole enhances ischaemia-induced arteriogenesis through an endocrine nitrite/nitric oxide-dependent pathway.
Dipyridamole enhances ischaemia-induced arteriogenesis through an endocrine nitrite/nitric oxide-dependent pathway.
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双嘧达莫通过内分泌亚硝酸盐/一氧化氮依赖性途径增强缺血诱导的动脉生成。
DOI：
10.1093/cvr/cvq002
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发表时间：
2010
影响因子：
10.8
通讯作者：
Kevil,ChristopherG
中科院分区：
文献类型：
--
作者：
Venkatesh,PrasannaK;Pattillo,ChristopherB;Branch,Billy;Hood,Jay;Thoma,Steven;Illum,Sandra;Pardue,Sibile;Teng,Xinjun;Patel,RakeshP;Kevil,ChristopherG
抗血小板药物，如双嘧达莫，对外周动脉疾病具有多种临床益处，推测其血管生成潜力可以保留缺血组织的活力，但双嘧达莫对缺血性动脉生成或血管生成的影响尚不清楚。在这里，我们检验了双嘧达莫治疗增强慢性缺血期间小动脉血管发育和功能的假设。方法和结果每天两次用 200 mg/kg 双嘧达莫治疗小鼠，以达到治疗血浆水平 (0.8–1.2 µg/mL)。通过永久性股动脉结扎诱导慢性后肢缺血，然后使用激光多普勒血流测量组织灌注以及血管密度、细胞增殖和一氧化氮（NO）代谢激活的量化。与对照治疗相比，双嘧达莫治疗迅速恢复缺血后肢血流，增加血管密度和细胞增殖，并增强侧支动脉灌注。双嘧达莫对血流和血管密度的有益作用取决于一氧化氮的产生，因为双嘧达莫不会增强内皮一氧化氮合酶（eNOS）缺陷小鼠的缺血组织再灌注、血管密度或内皮细胞增殖。与对照组和 eNOS−/− 小鼠相比，双嘧达莫治疗小鼠的血液和组织亚硝酸盐水平显着升高，证实了以 PKA 依赖性方式调节的 NO 产生增加。结论 双嘧达莫增加了亚硝酸盐/NO 产生，导致缺血肢体的动脉生成活性和血液灌注增强。总之，这些数据表明双嘧达莫可以增强缺血性血管功能并恢复血流，这可能有益于外周动脉疾病。
AimsAnti-platelet agents, such as dipyridamole, have several clinical benefits for peripheral artery disease with the speculation of angiogenic potential that could preserve ischaemic tissue viability, yet the effect of dipyridamole on ischaemic arteriogenesis or angiogenesis is unknown. Here we test the hypothesis that dipyridamole therapy augments arteriolar vessel development and function during chronic ischaemia.Methods and resultsMice were treated with 200 mg/kg dipyridamole twice daily to achieve therapeutic plasma levels (0.8–1.2 µg/mL). Chronic hindlimb ischaemia was induced by permanent femoral artery ligation followed by measurement of tissue perfusion using laser Doppler blood flow along with quantification of vascular density, cell proliferation, and activation of nitric oxide (NO) metabolism. Dipyridamole treatment quickly restored ischaemic hindlimb blood flow, increased vascular density and cell proliferation, and enhanced collateral artery perfusion compared with control treatments. The beneficial effects of dipyridamole on blood flow and vascular density were dependent on NO production as dipyridamole did not augment ischaemic tissue reperfusion, vascular density, or endothelial cell proliferation in endothelial NO synthase (eNOS)-deficient mice. Blood and tissue nitrite levels were significantly higher in dipyridamole-treated mice compared with controls and eNOS−/−mice, verifying increased NO production that was regulated in a PKA-dependent manner.ConclusionDipyridamole augments nitrite/NO production, leading to enhanced arteriogenesis activity and blood perfusion in ischaemic limbs. Together, these data suggest that dipyridamole can augment ischaemic vessel function and restore blood flow, which may be beneficial in peripheral artery disease.
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影响因子：
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DOI：
10.1530/jrf.0.0420121
发表时间：
1975-01-01
期刊：
JOURNAL OF REPRODUCTION AND FERTILITY
影响因子：
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作者：
LEE, VWK;DEKRETSER, DM;WANG, C
通讯作者：
WANG, C