Endothelin-1 Overexpression Improves Renal Function in eNOS Knockout Mice.
Cell Physiol Biochem
; 37(4): 1474-90, 2015.
Article
en En
| MEDLINE
| ID: mdl-26509263
BACKGROUND/AIMS: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. METHODS: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. RESULTS: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpine1, TIMP1, Col1a1, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. CONCLUSION: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in ß-oxidation of fatty acids) and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels).
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Endotelina-1
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Óxido Nítrico Sintasa de Tipo III
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Riñón
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell Physiol Biochem
Asunto de la revista:
BIOQUIMICA
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FARMACOLOGIA
Año:
2015
Tipo del documento:
Article