© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Evidence for P2-purinoceptors contribution in H2O2-induced contraction of rat aorta in the absence of endothelium
aDepartment of Pharmacology, School of Medicine, Zhejiang University, Hubin Campus, 353 Yanan Road, Hangzhou, 310031, PR China
bSmooth Muscle Research Program and Department of Medicine, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, Ontario L8 N 3Z5, Canada
* Corresponding author kwancy{at}fhs.mcmaster.ca
Objective: H2O2 can contract many arteries, however the underlying mechanisms are not fully understood. This study aims to test whether H2O2-induced vasoconstriction could be functionally attributed to the activation of P2-purinoceptors in rat aorta and to explore its possible signaling mechanisms. Methods: Isometric tension recording of H2O2 and ATP-induced contractions of rat aortic rings were compared in the absence or presence of various pharmacological tools to identify their possible common signaling pathways. Results: Both H2O2 and ATP induced transient phasic contractions in a concentration-dependent manner (1–1000 µM). Removal of endothelium potentiated the contractile responses to H2O2 and to ATP. H2O2 (30 µM)-induced phasic contraction could be abolished by catalase (800 U/ml), but not affected by SOD (150 U/ml), DMSO (5 mM) and apyrase (5 U/ml), suggesting no involvement of O2–, hydroxyl free radicals and ATP release. Also, several receptor antagonists including phentolamine, atropine, methysergide and chlorpheniramine (each 3 µM) were without effect on H2O2 (30 µM)-induced phasic contraction, suggesting no involvement of typical neurotransmitter release. However, both H2O2 (30 µM) and ATP (1 mM)-induced phasic contractions not only presented homologous desensitization, but also showed heterogeneous desensitization. Furthermore, the phasic contractions in response to H2O2 (30 µM) or ATP (100 µM) could be inhibited or abolished in a concentration dependent manner by RB-2 and suramin (10–100 µM), two widely used P2-purinoceptor antagonists, with only partial inhibition by Evans blue (300 µM), a moderately selective P2x receptor blocker, or by 
-β-methylene-ATP (100 µM), a selective P2x receptor desensitizer. On the other hand, both H2O2 (30 µM) and ATP (100 µM)-induced phasic contractions were also attenuated, to different degree, by inhibitors of several enzymes including PLC, PKC, PLA2 and cyclooxygenase. Lastly, removal of extracellular Ca2+ or pretreatment with procaine (10 mM) and dantrolene (30 µM), two putative intracellular Ca2+ release blockers, or with Ni2+ (100 µM) and tetrandrine (5 µM), two Ca2+ channel blockers, all significantly inhibited H2O2 and ATP-induced contractions. However, nifedipine (1 µM), a voltage-dependent L-type Ca2+ channel blocker, was without effect. Conclusions: Our results demonstrate that H2O2-induced phasic contraction of rat aorta involves, at least in part, the activation of P2-purinoceptors in the aortic smooth muscle cells
KEYWORDS Arteries; Endothelial receptors; Free radicals; Smooth muscle; Vasoconstriction/dilation
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