title: Downstream exposure to growth factors causes elevated velocity and dilation in arteriolar networks.
abstract: Our goal was to characterize changes in flow and diameter with vascular endothelial cell growth factor A (VEGF-A) and fibroblast growth factor 2 (FGF2). Observations were made in arteriolar networks of the cheek pouch tissue in anesthetized hamsters (pentobarbital 70 mg/kg, i.p., n = 45). Local and remote dilation responses to micropipette-applied VEGF or FGF2 yielded similar EC(50) values. The role of gap junctions in the remote response was tested by applying sucrose, halothane or 18αGA to the feed arteriole midway between the remote stimulation and upstream observation sites; all remote dilation to FGF2 was prevented, while only the early dilation to VEGF was blocked. The remote dilation to VEGF displayed a second rheologic mechanism. The second mechanism involved an abrupt increase in upstream velocity and shear rate, followed by nitro-arginine sensitive dilation. To test whether the abrupt increase in shear could be caused by other agents known to cause edema, remote responses to histamine and thrombin were tested. Each caused an abrupt increase in velocity followed by nitro-arginine-sensitive dilation. This study shows that VEGF or agents that increase permeability can initiate an upstream velocity increase with dilation that recruits flow to the network; this is in addition to simultaneous gap junction-mediated dilation.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794-5281, USA.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Georgi
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Dewar
authors.forename: Mary D
authors.initials: MD
authors.lastname: Frame
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D005109:Extracellular Matrix / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D008297:Male; D012212:Rheology; D033081:Shear Strength / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2