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Renal protective effects of induction of haem oxygenase‐1 combined with increased adiponectin on the glomerular vascular endothelial growth factor–nitric oxide axis in obese rats
Author(s) -
Liu Xue,
Zang Ping,
Han Fang,
Hou Ningning,
Sun Xiaodong
Publication year - 2015
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/ep085116
Subject(s) - endocrinology , medicine , vascular endothelial growth factor , adiponectin , nitric oxide , heme oxygenase , chemistry , nitric oxide synthase , endothelium , kidney , heme , biochemistry , insulin resistance , insulin , vegf receptors , enzyme
New FindingsWhat is the central question of this study? This study aimed to investigate whether induction of haem oxygenase‐1 (HO‐1) can protect the kidneys of obese rats by regulating the glomerular vascular endothelial growth factor–nitric oxide (VEGF–NO) axis by increasing the adiponectin concentrations.What is the main finding and its importance? Induction of HO‐1 reduces the degree of microalbuminuria and has renal protective effects by improving endothelial function and regulating the uncoupled glomerular VEGF–NO axis in diet‐induced obese rats. The mechanism may be related to increased activation of the HO‐1–adiponectin axis.The glomerular vascular endothelial growth factor–nitric oxide (VEGF–NO) axis plays a critical role in maintenance of normal kidney function in obesity. Induction of haem oxygenase‐1 (HO‐1) may result in a parallel increase in adiponectin secretion. The aim of this study was to investigate whether induction of HO‐1 could protect the kidneys of obese rats by regulating the glomerular VEGF–NO axis by increasing adiponectin levels. Rats received high‐fat diets and were injected with either cobalt protoporphyrin to induce HO‐1 or stannous protoporphyrin to inhibit HO‐1. Blood and urine samples were collected. Endothelial function was determined by measuring the endothelium‐dependent vasodilatation of the aorta. Renal tissues were collected for CD34 immunohistochemistry. The glomerular VEGF–NO axis and the AMP kinase–phosphoinositide 3‐kinase (PI3K)/Akt–endothelial nitric oxide synthase pathway were measured. Induction of HO‐1 by cobalt protoporphyrin decreased microalbuminuria, plasma free fatty acids, serum high‐sensitivity C‐reactive protein and malondialdehyde levels and increased serum adiponectin levels compared with the untreated obese rats. Severe impairment of endothelium‐dependent vasodilatation was observed in the obese rats, which was improved to some extent by HO‐1 induction. Induction of HO‐1 reduced glomerular CD34 expression and production of reactive oxygen species in obese rats. Obese rats showed increased glomerular VEGF expression and reduced NO levels. This uncoupling of the glomerular VEGF–NO axis was improved to some extent by induction of HO‐1, with enhancement of p‐AMP kinase, p‐Akt and phospho‐endothelial nitric oxide synthase in obese rats. These results indicate that induction of HO‐1 with cobalt protoporphyrin reduces the degree of microalbuminuria and has renal protective effects by improving endothelial dysfunction and regulating the glomerular VEGF–NO axis in diet‐induced obese rats by increasing adiponectin levels.