title: Spatial heterogeneity in VEGF-induced vasodilation: VEGF dilates microvessels but not epicardial and systemic arteries and veins.
abstract: This study was designed to investigate the site of vascular endothelial growth factor (VEGF)-induced vasodilation in the systemic and coronary vasculature. Intracoronary infusion of VEGF in Yorkshire pigs resulted in a significant drop in the mean arterial blood pressure, with a decline in the left ventricular left end-diastolic pressure, and no change in the heart rate. Coronary blood flow increase after intracoronary infusion of 10 mg VEGF (2.63 +/- 0.49x) was comparable to that seen after 40 mg of intracoronary adenosine (2.5 +/- 0.53x, p = 0.67) and was significantly higher then after 200 mg of intracoronary nitroglycerine (1.9 +/- 0.12x, p = 0.0005). At the same time, intracoronary VEGF did not result in a significant increase in coronary cross-sectional area determined using intravascular ultrasound. In vitro, VEGF produced dose-dependent relaxation of myocardial and systemic arterioles and venules (arterioles: 60-100 mm and venules: 120-200 mm in internal diameter) that was partially inhibited by L-NNA, but had no effect on epicardial coronary arteries, systemic arteries, or veins. Both VEGF receptors (flt-1 and flk-1) were identified on endothelial cells of epicardial arteries and veins. We conclude that this spatial heterogeneity of VEGF vasomotor effects cannot be explained by the absence VEGF receptors and suggests differential patterns of signal transduction in the vascular tree.
authors.affiliation: Angiogenesis Research Center, Department of Medicine and Surgery, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. rlaham@bidmc.harvard.edu
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Laham
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Motohisa
authors.initials: M
authors.lastname: Tofukuji
authors.forename: Mark
authors.initials: M
authors.lastname: Post
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents; D005996:Nitroglycerin; D000241:Adenosine