Vascular endothelial growth factor-mediated, endothelium-dependent relaxation in human internal mammary artery
Abstract
Vascular endothelial growth factor (VEGF) has been shown to have potential to treat ischemic diseases. Moreover, its vasorelaxing or vasodilatory effect might be favorable for relieving graft spasm. In this study, we examined the vasorelaxing effects of recombinant VEGF in isolated human internal mammary artery (IMA) and compared the responses to acetylcholine and nitroglycerin. Isometric tension of IMA ring segments was measured with an organ bath technique. With an optimal resting tension determined from its individual length-tension curve, precontraction was induced by 10(-8) M U46619 and cumulative concentration-relaxation was measured by application of VEGF (10(-12) to 10(-15) M), acetylcholine (10(-10) to 10(-5) M), and then nitroglycerin (10(-4.5) M). Vascular endothelial growth factor induced concentration-dependent relaxation (EC50: -9.89+/-0.05 log M; Emax: 63.2%+/-7.3%) in IMA with intact endothelium. The relaxant responses to VEGF were significantly attenuated by pretreatment with Nomega-nitro-L-arginine (L-NNA) alone and indomethacin + L-NNA, and totally abolished by removal of the endothelium or pretreatment with indomethacin + L-NNA + oxyhemoglobin. Internal mammary arteries became more sensitive to VEGF in the p...Continue Reading
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Vasodilator effect and mechanism of action of vascular endothelial growth factor in skin vasculature
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