Protective mechanism of adenosine to the rat arterial endothelial dysfunction induced by hydrogen peroxide.
This study was designed to examine the in vitro effects of adenosine (Ado) on hydrogen peroxide-induced endothelial dysfunction in rats. Endothelial dysfunction was induced by exposing isolated rat mesenteric arteries to hydrogen peroxide (0.5 mM) for 12 h using an organ culture system. The protective effects of adenosine were tested by exposing isolated mesenteric arteries to adenosine (3 x 10(-7) mol/l, 10(-6) mol/l, 3 x 10(-6) mol/l)+hydrogen peroxide (0.5 mM) for 12 h. This exposure to hydrogen peroxide induced a significant concentration-dependent inhibition of endothelium-dependent relaxation (EDR). Coculture of segments of mesenteric artery with adenosine (3 x 10(-7), 10(-6), and 3 x 10(-6) mol/l) attenuated the hydrogen peroxide-induced impairment of vasorelaxation. This impairment was accompanied by a reduction in nitrite/nitrate, nitric oxide (NO) synthase (NOS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and an increasing in malondislehyde (MDA) and lactate dehydrogenase (LDH) activities in the aorta. These results indicate that adenosine can be used to attenuate hydrogen peroxide-induced endothelial dysfunction, an effect that may be related to antioxidation, thus enhancing NO production by preventing the decrease in NOS.
Lu
Jun
J
Department of Pharmacology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Zhu
Shu-Ming
SM
Zang
Wei-Jin
WJ
Xu
Xiao-Li
XL
Luo
Hong-Li
HL
Yu
Xiao-Jiang
XJ
Wang
Sheng-Peng
SP
Kong
Shan-Shan
SS
Wu
Jie
J
Horie
Minoru
M
Sun
Lei
L
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006861:Hydrogen Peroxide / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D000241:Adenosine