Spatial heterogeneity in VEGF-induced vasodilation: VEGF dilates microvessels but not epicardial and systemic arteries and veins

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 mug VEGF (2.63 +/- 0.49x) was comparable to that seen after 40 mug of intracoronary adenosine (2.5 +/- 0.53x, p = 0.67) and was significantly higher then after 200 mug 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 mum and venules: 120-200 mum 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.