Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats

Salsoso, Rocío, Guzman-Gutierrez, Enrique, Arroyo, Pablo, Salomon, Carlos, Zambrano, Sonia, Victoria Ruiz-Armenta, María, Blanca, Antonio Jesús, Pardo, Fabián, Leiva, Andrea, Mate, Alfonso, Sobrevia, Luis and Vazquez, Carmen María (2014) Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats. PLoS ONE, 9 2: . doi:10.1371/journal.pone.0090339

Author Salsoso, Rocío
Guzman-Gutierrez, Enrique
Arroyo, Pablo
Salomon, Carlos
Zambrano, Sonia
Victoria Ruiz-Armenta, María
Blanca, Antonio Jesús
Pardo, Fabián
Leiva, Andrea
Mate, Alfonso
Sobrevia, Luis
Vazquez, Carmen María
Title Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2014-02-28
Year available 2014
Sub-type Article (original research)
DOI 10.1371/journal.pone.0090339
Open Access Status DOI
Volume 9
Issue 2
Total pages 11
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+dep) compared with Na+-independent (Na+indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (Vmax), without changes in apparent Km for Na+indep transport in SHR compared with WKY rats. Total and Na+dep component of transport were increased, but Na+indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced L-carnitine transport (likely via Na+-dependent Octn2) could limit this compound's potential beneficial effects in RAECs from SHR.
Keyword Hypertension
Endothelial cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes online open access article: e90339

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2015 Collection
Faculty of Medicine
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