NDT Advance Access published online on September 22, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl443
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratory of Vascular Medicine, University Medical Centre Utrecht, Institute and Graduate School of Biomembranes, Utrecht, The Netherlands; Department of Nephrology and Hypertension, University Medical Centre Utrecht, Institute and Graduate School of Biomembranes, Utrecht, The Netherlands
* To whom correspondence should be addressed. Background. Hypoalbuminaemia is associated with increased risk of cardiovascular disease. It is unclear whether endothelial dysfunction is a direct result of low albumin or whether it is caused by factors like chronic inflammation or dyslipidaemia. In this study, the effect of low albumin concentrations on endothelial nitric oxide synthase (eNOS)-dependent NO production was determined in vitro and ex vivo. Methods. eNOS activity, assessed by arginine-citrulline conversion, and NO production, determined by 4,5-diaminofluorescein diacetate, electron paramagnetic resonance and Griess colorimetry, were measured in cultured endothelial cells expressing high levels of eNOS (bEnd.3) after exposure to albumin concentrations ranging from 0.5 mmol/l (33 g/l) to 0 mmol/l. Analbuminaemic and control rat plasma NO metabolites and aortic eNOS protein mass were determined, and aortic endothelium-independent and endothelium-dependent vasodilator tone were measured ex vivo under albumin-free conditions. Results. In vitro, eNOS activity was significantly increased in the absence of albumin (75 ± 2 vs 26 ± 6 pmol/min/mg protein; P < 0.01). Low albumin levels consistently increased NO production in endothelial cells. Plasma NO metabolites were increased (18.2 ± 1.9 vs 12.5 ± 0.8 µmol/l; P < 0.05) and endothelium-independent relaxation was markedly blunted in analbuminaemic rats, resulting in a considerably higher ED50 (80 ± 2 vs 1.1 ± 0.2 nmol/l, P < 0.01), while endothelium-dependent dilatation was slightly, but significantly, increased. Aortic eNOS protein mass was not affected. This implies that in vivo hypoalbuminaemia reduces vascular NO sensitivity. Conclusion. We show that low albumin as such seems to enhance, rather than diminish, eNOS-mediated endothelial NO production.
Received June 16, 2006
Accepted June 26, 2006
Original Article
Low albumin levels increase endothelial NO production and decrease vascular NO sensitivity
Lonneke M. Bevers 1, Ernst E. van Faassen 2, Thi Danh Vuong 3, Zhenmin Ni 4, Peter Boer 3, Hein A. Koomans 3, Branko Braam 3, Nosratola D. Vaziri 4, and Jaap A. Joles 3 *
2 Faculty of Science, Section Interface Physics, Utrecht University, Utrecht, The Netherlands
3 Department of Nephrology and Hypertension, University Medical Centre Utrecht, Institute and Graduate School of Biomembranes, Utrecht, The Netherlands
4 Division of Nephrology and Hypertension, Departments Medicine, Physiology and Biophysics, University of California, Irvine, USA
Jaap A. Joles, E-mail: J.A.Joles{at}med.uu.nl
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. E. Rubio-Ruiz, E. Diaz-Diaz, M. Cardenas-Leon, R. Arguelles-Medina, P. Sanchez-Canales, F. Larrea-Gallo, E. Soria-Castro, and V. Guarner-Lans Glycation does not modify bovine serum albumin (BSA)-induced reduction of rat aortic relaxation: The response to glycated and nonglycated BSA is lost in metabolic syndrome Glycobiology, July 1, 2008; 18(7): 517 - 525. [Abstract] [Full Text] [PDF]
|
|