Hydrogen peroxide increases nerve-evoked contractions in mouse tail artery by an endothelium-dependent mechanism

Reactive oxygen species contribute to regulating the excitability of vascular smooth muscle. This study investigated the actions of the relatively stable reactive oxygen species, H(2)O(2), on nerve-evoked contractions of mouse distal tail artery. H(2)O(2) (10-100 μM) increased nerve-evoked contractions of isometrically mounted segments of tail artery. Endothelium denudation increased nerve-evoked contractions and abolished the facilitatory effect of H(2)O(2). Inhibition of nitric oxide synthase with L-nitroarginine methyl ester (0.1mM) also increased nerve-evoked contractions and reduced the late phase of H(2)O(2)-induced facilitation. H(2)O(2)-induced facilitation of nerve-evoked contractions depended, in part, on synthesis of prostanoids and was reduced by the cyclooxygenase inhibitor indomethacin (1 μM) and the thromboxane A(2) receptor antagonist SQ 29548 (1 μM). H(2)O(2) increased sensitivity of nerve-evoked contractions to the α(2)-adrenoceptor antagonist idazoxan (0.1 μM) but not to the α(1)-adrenoceptor antagonist prazosin (10nM). Idazoxan and the α(2C)-adrenoceptor antagonist JP 1302 (0.5-1 μM) reduced H(2)O(2)-induced facilitation. H(2)O(2) induced facilitation of nerve-evoked contractions was abolished by the non-selective cation channel blocker SKF-96365 (10 μM), suggesting it depends on Ca(2+) influx. In conclusion, H(2)O(2)-induced increases in nerve-evoked contractions depended on an intact endothelium and were mediated by activating thromboxane A(2) receptors and by increasing the contribution of α(2)-adrenoceptors to these responses.