Vasodilator effect and mechanism of action of vascular endothelial growth factor in skin vasculature

Vasodilator effect and mechanism of action of vascular endothelial growth factor in skin vasculature
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DOI:
10.1152/ajpheart.00901.2003
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发表时间:
2004-03-01
影响因子:
4.8
通讯作者:
Pang, CY
Pang, CY
中科院分区:
医学2区
文献类型:
--
作者:
Ashrafpour, H;Huang, N;Pang, CY

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多个实验室报道,手术时局部皮下或皮下注射VEGF(165)可有效减轻大鼠皮瓣的缺血性坏死,但尚未研究其机制,并暗示血管生成会增强。在本研究中,我们使用临床相关的分离灌注6x16厘米猪臀部皮瓣模型来1)检验我们的假设,即VEGF(165)是一种有效的血管扩张剂,并且急性VEGF(165)治疗会增加皮肤灌注; 2)研究VEGF(165)诱导皮肤血管舒张的机制。我们观察到,在用次最大浓度的去甲肾上腺素 (NE)、内皮素-1 或 U-46619 预收缩的皮瓣中,VEGF(165) (5x10(-16)-5x10(-11) M) 会引起浓度依赖性的灌注压下降(即血管舒张)。使用皮肤荧光测定技术评估皮肤灌注,证实了 VEGF(165) 诱导的皮肤血管舒张。 NE预缩皮瓣中VEGF(165)的血管舒张功效(pD(2)=13.57+/-0.31)更高(P
Various laboratories have reported that local subcutaneous or subdermal injection of VEGF(165) at the time of surgery effectively attenuated ischemic necrosis in rat skin flaps, but the mechanism was not studied and enhanced angiogenesis was implicated. In the present study, we used the clinically relevant isolated perfused 6x16-cm pig buttock skin flap model to 1) test our hypothesis that VEGF(165) is a potent vasodilator and acute VEGF(165) treatment increases skin perfusion; and 2) investigate the mechanism of VEGF(165)-induced skin vasorelaxation. We observed that VEGF(165) (5x10(-16)-5x10(-11) M) elicited a concentration-dependent decrease in perfusion pressure (i.e., vasorelaxation) in skin flaps preconstricted with a submaximal concentration of norepinephrine (NE), endothelin-1, or U-46619. The VEGF(165)-induced skin vasorelaxation was confirmed using a dermofluorometry technique for assessment of skin perfusion. The vasorelaxation potency of VEGF(165) in NE-preconstricted skin flaps (pD(2)=13.57+/-0.31) was higher (P