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
Subject 1100 Agricultural and Biological Sciences
1300 Biochemistry, Genetics and Molecular Biology
2700 Medicine
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 nonhypertensive 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 endotheliumdependent 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.
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
Aorta
Endothelium
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID FONDECYT 1110977
Anillos ACT-73
AT-24120944
PI 0034/2008
C/024225/09
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
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Faculty of Medicine
 
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