Journal article
Chronic renal failure alters endothelial function in cerebral circulation in mice
American journal of physiology. Heart and circulatory physiology, Vol.301(3), pp.H1143-H1152
09/2011
DOI: 10.1152/ajpheart.01237.2010
PMID: 21705678
Abstract
We examined structure, composition, and endothelial function in cerebral arterioles after 4 wk of chronic renal failure (CRF) in a well-defined murine model (C57BL/6J and apolipoprotein E knockout female mice). We also determined quantitative expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (on serine 1177 and threonine 495), and caveolin-1; quantitative expression of markers of vascular inflammation or oxidative stress [Rock-1, Rock-2, VCAM-1, and peroxisome proliferator-activated receptor-γ (PPARγ)]; and the plasma concentration of l-arginine and asymmetric dimethylarginine (ADMA). Our hypothesis was that endothelial function would be impaired in cerebral arterioles during CRF following either a decrease in NO production (through alteration of eNOS expression or regulation) or an increase in NO degradation (due to oxidative stress or vascular inflammation). Endothelium-dependent relaxation was impaired during CRF, but endothelium-independent relaxation was not. CRF had no effect on cerebral arteriolar structure and composition. Quantitative expressions of eNOS, eNOS phosphorylated on serine 1177, caveolin-1, Rock-1, Rock-2, and VCAM-1 were similar in CRF and non-CRF mice. In contrast, quantitative expression of PPARγ (which exercises a protective role on blood vessels) was significantly lower in CRF mice, whereas quantitative expression of eNOS phosphorylated on the threonine 495 (the inactive form of eNOS) was significantly higher. Lastly, the plasma concentration of ADMA (a uremic toxin and an endogenous inhibitor of eNOS) was elevated and plasma concentration of l-arginine was low in CRF. In conclusion, endothelial function is impaired in a mouse model of early stage CRF. These alterations may be related (at least in part) to a decrease in NO production.
Details
- Title: Subtitle
- Chronic renal failure alters endothelial function in cerebral circulation in mice
- Creators
- Jean-Marc Bugnicourt - Institut National de la Santé et de la Recherche Médicale, ERI12;, Services de 3Neurologie andCharlène Da Silveira - Institut National de la Santé et de la Recherche Médicale, ERI12;, Université de Picardie Jules Verne, Amiens, FranceAbderrahmane Bengrine - Université de Picardie Jules VerneOlivier Godefroy - Université de Picardie Jules VerneGary Baumbach - University of IowaHenri Sevestre - Université de Picardie Jules VerneStefanie M Bode-Boeger - Institute for Clinical Pharmacology, Otto von Guericke University, Magdeburg; andJan T Kielstein - Medizinische Hochschule HannoverZiad A Massy - Université de Picardie Jules VerneJean-Marc Chillon - Institut National de la Santé et de la Recherche Médicale, ERI12;, Université de Picardie Jules Verne, Amiens, France
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Heart and circulatory physiology, Vol.301(3), pp.H1143-H1152
- DOI
- 10.1152/ajpheart.01237.2010
- PMID
- 21705678
- ISSN
- 0363-6135
- eISSN
- 1522-1539
- Language
- English
- Date published
- 09/2011
- Academic Unit
- Pathology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984186619602771
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