Vascular endothelial growth factor-mediated, endothelium-dependent relaxation in human internal mammary artery.
BACKGROUND
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.


METHODS
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).


RESULTS
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 presence of indomethacin alone. However, acetylcholine-induced relaxation was not abolished by treatment with indomethacin + L-NNA + oxyhemoglobin (Emax: 16.9%+/-2.7%). The endothelium-independent relaxations induced by nitroglycerin were also significantly inhibited by administration of oxyhemoglobin.


CONCLUSIONS
The results demonstrate that VEGF-induced endothelium-dependent relaxation in the human IMA is mainly due to nitric oxide release. Although the vasorelaxing effect is not the primary advantage of this drug when it is used for angiogenesis, such effect may be advantageous in patients who also need a coronary artery bypass operation.
Liu
Ming-Hui
MH
Cardiovascular Research, Starr Academic Center, St. Vincent Heart Institute, Department of Surgery, Oregon Health Sciences University, Portland, USA.
Jin
Hongkui
H
Floten
H Storm
HS
Ren
Zhev
Z
Yim
Anthony P C
AP
He
Guo-Wei
GW
D000368:Aged; D016228:Endothelial Growth Factors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000502:physiology*; D008297:Male; D008323:Mammary Arteries; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000502:physiology*
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009569:Nitric Oxide; D005996:Nitroglycerin