Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric sxide pathways

Cabrera, Lissette, Saavedra, Andrea, Rojas, Susana, Cid, Marcela, Valenzuela, Cristina, Gallegos, David, Careaga, Pamela, Basualto, Emerita, Haensgen, Astrid, Pena, Eduardo, Rivas, Coralia, Carlos Vera, Juan, Gallardo, Victoria, Zuniga, Leandro, Escudero, Carlos, Sobrevia, Luis, Wareing, Mark and Gonzalez, Marcelo (2016) Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric sxide pathways. Frontiers in Physiology, 7 NOV: . doi:10.3389/fphys.2016.00529


Author Cabrera, Lissette
Saavedra, Andrea
Rojas, Susana
Cid, Marcela
Valenzuela, Cristina
Gallegos, David
Careaga, Pamela
Basualto, Emerita
Haensgen, Astrid
Pena, Eduardo
Rivas, Coralia
Carlos Vera, Juan
Gallardo, Victoria
Zuniga, Leandro
Escudero, Carlos
Sobrevia, Luis
Wareing, Mark
Gonzalez, Marcelo
Title Insulin induces relaxation and decreases hydrogen peroxide-induced vasoconstriction in human placental vascular bed in a mechanism mediated by calcium-activated potassium channels and L-arginine/nitric sxide pathways
Journal name Frontiers in Physiology   Check publisher's open access policy
ISSN 1664-042X
Publication date 2016-11-22
Sub-type Article (original research)
DOI 10.3389/fphys.2016.00529
Open Access Status DOI
Volume 7
Issue NOV
Total pages 13
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Collection year 2017
Language eng
Formatted abstract
Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1) and nitric oxide synthesis (NO) in human umbilical vein endothelial cells (HUVECs). Short-term effects of insulin on vasculature have been reported in healthy subjects and cell cultures; however, its mechanisms remain unknown. The aim of this study was to characterize the effect of acute incubation with insulin on the regulation of vascular tone of placental vasculature. HUVECs and chorionic vein rings were isolated from normal pregnancies. The effect of insulin on NO synthesis, L-arginine transport, and hCAT-1 abundance was measured in HUVECs. Isometric tension induced by U46619 (thromboxane A2 analog) or hydrogen peroxide (H2O2) were measured in vessels previously incubated 30 min with insulin and/or the following pharmacological inhibitors: tetraethylammonium (KCa channels), iberiotoxin (BKCa channels), genistein (tyrosine kinases), and wortmannin (phosphatidylinositol 3-kinase). Insulin increases L-arginine transport and NO synthesis in HUVECs. In the placenta, this hormone caused relaxation of the chorionic vein, and reduced perfusion pressure in placental cotyledons. In vessels pre-incubated with insulin, the constriction evoked by H2O2 and U46619 was attenuated and the effect on H2O2-induced constriction was blocked with tetraethylammonium and iberiotoxin, but not with genistein, or wortmannin. Insulin rapidly dilates the placental vasculature through a mechanism involving activity of BKCa channels and L-arginine/NO pathway in endothelial cells. This phenomenon is related to quick increases of hCAT-1 abundance and higher capacity of endothelial cells to take up L-arginine and generate NO.
Keyword Insulin
L-arginine
Nitric oxide
HCAT-1
BKCa channels
Placenta
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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