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Gao YJ, Hirota S, Zhang DW, Janssen LJ, Lee RM: Mechanisms of hydrogen-peroxide-induced biphasic response in rat mesenteric artery. Br J Pharmacol. 2003 Mar;138(6):1085-92.
1. In phenylephrine (PHE) (1 micro M)-precontracted superior mesenteric arteries from adult rats, low concentration of hydrogen peroxide (H (2) O (2), 10-100 micro M) caused only contraction, while high concentration of H (2) O (2) (0.3-1 mM) caused a biphasic response: a transient contraction followed by a relaxation response. 2. Endothelium removal did not affect the biphasic response. 7,7-Dimethyl-(5Z,8Z)-eicosadienoic acid, diclofenac, furegrelate, or SQ 29548 greatly inhibited the contraction but did not affect the relaxation. 17-Octadecynoic acid, eicosatriynoic acid, ICI 198615, SQ 22536, or ODQ did not inhibit the biphasic response. 3. KCl at 40 mM inhibited the relaxation response to H (2) O (2) by 98+/-24%. 4-Aminopyridine (4-AP) inhibited while tetraethylammonium chloride (TEA), charybdotoxin, or glibenclamide attenuated the relaxation response. A combination of 4-AP, TEA and glibenclamide mimicked the effects of 40 mM KCl. Iberiotoxin, apamin, or barium chloride did not inhibit the relaxation response. 4. H (2) O (2) at 1 mM hyperpolarized membrane potential and reversibly augmented K (+) current in smooth muscle cells of mesenteric artery. These effects of H (2) O (2) were attenuated significantly by 4-AP. 5. In summary, in PHE-precontracted rat mesenteric artery: (1) the response to H (2) O (2) shifted qualitatively from contraction to a biphasic response as H (2) O (2) increased to 0.3 mM or higher; (2) the relaxation response is caused by the activation of K (+) channels, with voltage-dependent K (+) channels playing a primary role; and the contraction is likely to be mediated by thromboxane A (2); (3) the K (+) channel activation by H (2) O (2) is independent of phospholipase A (2), cyclooxygenase, lipoxygenase, cytochrome P450 monooxygenase, adenylate or guanylate cyclase. |
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