title: Endothelial-derived hyperpolarization factor (EDHF) contributes to PlGF-induced dilation of mesenteric resistance arteries from pregnant rats.
abstract: The aim of this study was to investigate the cellular mechanism involved in the potent vasodilatory action of PlGF on mesenteric resistance arteries from pregnant rats. PlGF (3 nM) induced a vasodilation of 64 ± 3.8% that was completely abolished by endothelial denudation. Significant dilation (28 ± 4.0%) remained, however, in the presence of nitric oxide synthase and cyclooxygenase inhibition, and was associated with significant reductions in vascular smooth muscle cell calcium. Absence of dilation in potassium-depolarizing solution (30 mM) confirmed its dependence on endothelial-derived hyperpolarization factor. Subsequent studies established that vasodilation was abolished by pharmacologic inhibition of SK(Ca) (apamin) and BK(Ca) (iberiotoxin) but not IK(Ca) (tram-34) potassium channels. In summary, PlGF acts through the release of a combination of endothelium-derived relaxation factors. Based on the results of potassium channel blockade, we suggest that it induces endothelial hyperpolarization via SK(Ca) channel activation; this, in turn, leads to the release of a diffusible mediator that activates vascular smooth muscle BK(Ca) channels, hyperpolarization and vasodilation. This is the first study to identify the mechanism for PlGF/VEGFR-1 resistance artery dilation in the pregnant state, whose attenuation likely contributes to the systemic hypertension characteristic of pre- eclampsia.
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont, College of Medicine, Burlington, Vt. 05405, USA. maurizio.mandala @ uvm.edu
authors: Maurizio
authors: M
authors: Mandalà
authors: Natalia
authors: N
authors: Gokina
authors: Carolyn
authors: C
authors: Barron
authors: George
authors: G
authors: Osol
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D000072483:Placenta Growth Factor; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D001685:Biological Factors; C000608038:Pgf protein, rat; D024681:Potassium Channels, Calcium-Activated; D011257:Pregnancy Proteins; C067410:endothelium-dependent hyperpolarization factor; D018999:Charybdotoxin; D000072483:Placenta Growth Factor; D001030:Apamin; D040281:Vascular Endothelial Growth Factor Receptor-1; D000109:Acetylcholine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester