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.
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 (SnCl(2)) to upregulate HO-1. Treatment with SnCl(2) 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.
Cao
Jian
J
Department of Pharmacology, New York Medical College, Valhalla, NY 10595 USA.|Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853 China.
Drummond
George
G
Department of Pharmacology, New York Medical College, Valhalla, NY 10595 USA.
Inoue
Kazuyoshi
K
Department of Pharmacology, New York Medical College, Valhalla, NY 10595 USA.
Sodhi
Komal
K
Department of Pharmacology, New York Medical College, Valhalla, NY 10595 USA.
Li
Xiao Ying
XY
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing 100853 China.
Omura
Shinji
S
Department of Pharmacology, New York Medical College, Valhalla, NY 10595 USA.