Upregulation of Heme Oxygenase-1 Combined with Increased Adiponectin Lowers Blood Pressure in Diabetic Spontaneously Hypertensive Rats through a Reduction in Endothelial Cell Dysfunction, Apoptosis and Oxidative Stress

International Journal of Molecular Sciences

Jian Cao²  George Drummond²  Kazuyoshi Inoue²  Komal Sodhi²  Xiao Ying Li¹ 

[1] Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853 China. E-Mail:;Department of Pharmacology, New York Medical College, Valhalla, NY 10595 USA. E-Mails:

关键词: Heme oxygenase;    hypertension;    diabetes;    adiponectin;    oxidative stress;    apoptosis;   

DOI  :  10.3390/ijms9122388

来源: mdpi

【 摘 要 】

This study was designed to investigate the effect of increased levels of HO-1 on hypertension exacerbated by diabetes. Diabetic spontaneously hypertensive rat (SHR) and WKY (control) animals were treated with streptozotocin (STZ) to induce diabetes and stannous chloride (SnCl₂) to upregulate HO-1. Treatment with SnCl₂ not only attenuated the increase of blood pressure (p<0.01), but also increased HO-1 protein content, HO activity and plasma adiponectin levels, decreased the levels of superoxide and 3-nitrotyrosine (NT), respectively. Reduction in oxidative stress resulted in the increased expression of Bcl-2 and AKT with a concomitant reduction in circulating endothelial cells (CEC) in the peripheral blood (p<0.005) and an improvement of femoral reactivity (response to acetylcholine). Thus induction of HO-1 accompanied with increased plasma adiponectin levels in diabetic hypertensive rats alters the phenotype through a reduction in oxidative stress, thereby permitting endothelial cells to maintain an anti-apoptotic environment and the restoration of endothelial responses thus preventing hypertension.

【 授权许可】

CC BY   
© 2008 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).