From the Department of Medicine, Teikyo University School of Medicine,
Tokyo (S.T., T.I., M.O., K.E., T.S.); the Department of Physiology, Tokai
University School of Medicine, Isehara (H.M., E.T.); and the Central Research
Laboratory, Hitachi Ltd., Tokyo (K.U.), Japan.
Correspondence to Satoshi Takeshita, MD, Department of Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo 173-8605, Japan. E-mail stake{at}blue.ocn.ne.jp
Background—Recent investigations
have demonstrated the ability of vascular endothelial
growth factor (VEGF) to augment the development of collateral arteries
in vivo. In vitro studies have suggested that the use of VEGF also
improves the endothelium-dependent relaxation of
collaterals at the microvascular level. The purpose of this study was
to determine in vivo the extent to which vasomotor responses of
collateral microvessels are altered after VEGF treatment.
Methods and Results—Ischemia was induced in the hindlimb
of 35 rats by excision of the femoral artery. Immediately thereafter,
400 µg of a plasmid encoding VEGF or ß-galactosidase (control) was
transfected into limb muscles. Four weeks later, synchrotron radiation
microangiography, with a spatial resolution of 30 µm, was
performed to document the reactivity of collateral microvessels.
Administration of the endothelium-dependent vasodilator
acetylcholine failed to induce dilation of collateral microvessels in
control animals. By contrast, profound dilation of collaterals was
observed after acetylcholine in VEGF-treated animals. This response was
evident in vessels with a linear appearance but not in those with an
undulating appearance. The resulting blood flow in the ischemic
limb after administration of acetylcholine in the control animals was
only 64.6±17.0% of that of the contralateral normal limb, whereas
blood flow was augmented to 106.1±8.4% in VEGF-treated animals
(P<0.05).
Conclusions—These results demonstrate in vivo that the use of
VEGF restores impaired vasomotor responses in some types of collateral
microvessels, which may help to provide a basis for understanding the
microcirculation after therapeutic angiogenesis with VEGF.
© 1998 American Heart Association, Inc.
Brief Rapid Communications
Endothelium-Dependent Relaxation of Collateral Microvessels After Intramuscular Gene Transfer of Vascular Endothelial Growth Factor in a Rat Model of Hindlimb Ischemia
Key Words: angiogenesis • collateral circulation • endothelium • microcirculation
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