Differential contractile actions of reactive oxygen species on rat aorta: selective activation of ATP receptor by H2O2.
This study aims to examine the effects of different reactive oxygen species (ROS) on the resting tension of endothelium-denuded rat aortic rings. In these preparations, H2O2 (30 microM) induced a fast and transient contraction, which could be abolished by pretreatment of catalase (800 U/ml), but not affected by superoxide anion scavenger, superoxide dismutase (SOD; 150 U/ml) or the hydroxyl free radical scavenger, DMSO/mannitol (each 3 mM). In contrast, pyrogallol, a putative superoxide anion donor, induced a biphasic contraction, which could be abolished by SOD, but not by catalase or DMSO/mannitol. Unlike H2O2 and pyrogallol, Vitamin C(VitC)/Fe2+ (each 100 microM), a commonly used hydroxyl radical-generating system, triggered a tonic contraction which could be prevented by DMSO/mannitol, but not by SOD or catalase. Interestingly, H2O2-induced contraction could be concentration-dependently (10-100 microM) inhibited by suramin and reactive blue-2 (RB-2), two widely used ATP receptor antagonists. On the other hand, suramin or RB-2, at concentration up to 100 microM, affected neither pyrogallol nor VitC/Fe2+-induced contraction. In conclusion, we showed for the first time that different ROS could contract rat aorta with different mechanisms of action, and H2O2 elicits a transient contraction probably as a result of the ATP receptor activation.
Shen
J Z
JZ
Department of Pharmacology, Faculty of Medicine, Zhejiang University, Hangzhou, PR China.
Zheng
X F
XF
Kwan
C Y
CY
D000818:Animals; D001011:Aorta; D001205:Ascorbic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011748:Pyrogallol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D005296:Ferrous Compounds; D017382:Reactive Oxygen Species; D018048:Receptors, Purinergic P2; D014227:Triazines; D011748:Pyrogallol; C012842:Cibacron Blue F 3GA; D013498:Suramin; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid