title: Platelet-derived growth factor (PDGF)-BB produces NO-mediated relaxation and PDGF receptor β-dependent tonic contraction in murine iliac lymph vessels.
abstract: We studied the effects of PDGF-BB on changes in the diameters of murine lymph vessels with or without intact endothelium. PDGF-BB induced dilation of the lymph vessels with endothelium. Pretreatment with l-NAME or removal of the endothelium caused a significant attenuation in the PDGF-BB-induced dilation. PDGF-BB also produced dose-related reduction of the diameters of the lymph vessels without endothelium. To evaluate intracellular signal transduction and Ca(2+) -dependence of the PDGF-BB-induced tonic contraction, we investigated the effects of imatinib, GW5074 (an inhibitor of Raf-1 kinase), U-73122 (an inhibitor of phospholipase C), and xestospongin C on the PDGF-BB-induced reduction responses. All of these inhibitors caused a significant attenuation in the PDGF-BB-induced reduction response that was significantly decreased by treatment with Ca(2+) -free Krebs-bicarbonate solution or nifedipine. Higher concentrations of PDGF-BB produced a marked reduction of lymph vessel diameter within both high K(+) Krebs-bicarbonate solution and Ca(2+) -free high K(+) Krebs solution containing 1mM EGTA. These findings suggest that PDGF-BB induced endothelium-dependent NO-mediated relaxation of lymphatic smooth muscles in murine lymph vessels. PDGF receptor β-mediated tonic contraction of the muscles through increased Ca(2+) influx through the membrane and the release of membrane-bound and intracellular Ca(2+) .
authors.affiliation: Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Maejima
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kawai
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ajima
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohhashi
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D002118:Calcium / Q000378:metabolism; D004729:Endothelium, Lymphatic / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D042601:Lymphatic Vessels / Q000502:physiology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D017479:Receptors, Platelet-Derived Growth Factor / Q000819:agonists / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D043925:Angiogenesis Inducing Agents; D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D009569:Nitric Oxide; D017479:Receptors, Platelet-Derived Growth Factor; D011188:Potassium; D002118:Calcium