title: Placental growth factor is a potent vasodilator of rat and human resistance arteries.
abstract: The objectives of this study were to determine whether placental growth factor (PlGF) exerts a vasodilatory effect on rat uterine vessels (arcuate arteries and veins) and to examine regional differences in reactivity by comparing these responses to those of comparably sized mesenteric vessels. We also sought to examine and compare its effects on human uterine and subcutaneous vessels. All vessels were studied in vitro, under pressurized (rat) or isometric wire-mounted (human) conditions, and exposed to a range of PlGF concentrations. Inhibitors of nitric oxide and prostaglandin synthesis were included in an effort to understand the causal mechanism(s). In rat uterine arteries, the effects of receptor inhibition and activation using selective ligands for VEGFR-1 (PlGF) vs. VEGFR-2 (VEGF-E) were determined, and real-time RT-PCR was performed to evaluate the effect of pregnancy on relative abundance of VEGFR-1 and VEGFR-2 message in the vascular wall. PlGF was a potent vasodilator of all vessels studied, with greatest sensitivity observed in rat uterine arteries. Pregnancy significantly augmented dilator sensitivity to PlGF, and this effect was associated with selective upregulation of VEGFR-1 message in the pregnant state. The contribution of nitric oxide was appreciable in rat and human uterine arteries, with lesser effects in rat uterine veins and mesenteric arteries, and with no observable effect in human subcutaneous vessels. Based on these results, we conclude that PlGF is a potent vasodilator of several vessel types in both humans and rats. Its potency and mechanism vary with physiological state and vessel location and are mediated solely by the VEGFR-1 receptor subtype. Gestational changes in the uterine circulation suggest that this factor may play a role in modulating uterine vascular remodeling and blood flow during the pregnant state.
authors.affiliation: Department of Obstetrics and Gynecology, University of Vermont College of Medicine, Burlington, VT 05405, USA. george.osol@uvm.edu
authors.forename: George
authors.initials: G
authors.lastname: Osol
authors.forename: Gerard
authors.initials: G
authors.lastname: Celia
authors.forename: Natalia
authors.initials: N
authors.lastname: Gokina
authors.forename: Carolyn
authors.initials: C
authors.lastname: Barron
authors.forename: Edward
authors.initials: E
authors.lastname: Chien
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mandala
authors.forename: Leonid
authors.initials: L
authors.lastname: Luksha
authors.forename: Karolina
authors.initials: K
authors.lastname: Kublickiene
mesh_terms: D000328:Adult; D000818:Animals; D001158:Arteries / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D009215:Myometrium / Q000098:blood supply; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014599:Uterus / Q000737:chemistry; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents; D014680:Veins / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; C000608036:PGF protein, human; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D014665:Vasodilator Agents; D000072483:Placenta Growth Factor; D019001:Nitric Oxide Synthase; D040262:Receptors, Vascular Endothelial Growth Factor; D019331:NG-Nitroarginine Methyl Ester