Hydrogen peroxide acts as an EDHF in the piglet pial vasculature in response to bradykinin
Hydrogen peroxide acts as an EDHF in the piglet pial vasculature in response to bradykinin
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DOI：
10.1152/ajpheart.00007.2002
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发表时间：
2002-07-01
影响因子：
4.8
通讯作者：
Busija, DW
中科院分区：
文献类型：
--
作者：
Lacza, Z;Puskar, M;Busija, DW
本研究探讨了缓激肽（BK）对EDHF介导的软膜动脉扩张的作用机制。在给予N-ω-硝基-L-精氨酸甲酯（L-NAME）和吲哚美辛后，局部应用BK（3 mumol/l）诱导血管舒张（62 +/- 12%），这可被内皮损伤或BK 2受体拮抗剂HOE-140（0.3 mumol/l）抑制。Western印迹法显示BK 2受体存在于大脑皮层和软脑膜血管组织样品中。细胞色素P-450拮抗剂咪康唑（20 μ mol/l）和脂氧合酶抑制剂黄芩素（10 μ mol/l）和肉桂酰-3，4-二羟基-α-氰基肉桂酸酯（1 μ mol/l）未能减少BK诱导的扩张。然而，H2 O2清除剂过氧化氢酶（400 U/ml）消除了反应（从54 +/- 11到0 +/- 2 μ m; P < 0.01）。ATP依赖性K+（K-ATP）通道抑制剂格列本脲（10 μ mol/l）也有类似的作用（从54 +/- 11到16 +/- 5 μ m; P < 0.05）。共同应用钙依赖性钾通道抑制剂charybdotoxin（0.1 μ mol/l）和apamin（0.5 μ mol/l）未能减少反应。我们的结论是，过氧化氢介导的非一氧化氮，非前列腺素依赖性血管舒张BK在小猪软脑膜血管。该反应通过BK 2受体和K-ATP通道的开放介导。
We investigated the mechanism of EDHF-mediated dilation to bradykinin (BK) in piglet pial arteries. Topically applied BK (3 mumol/l) induced vasodilation (62 +/- 12%) after the administration of N-omega-nitro-L-arginine methyl ester (L-NAME) and indomethacin, which was inhibited by endothelial impairment or by the BK2 receptor antagonist HOE-140 (0.3 mumol/l). Western blotting showed the presence of BK2 receptors in brain cortex and pial vascular tissue samples. The cytochrome P-450 antagonist miconazole (20 mumol/l) and the lipoxygenase inhibitors baicalein (10 mumol/l) and cinnamyl-3,4-dyhydroxy-alpha-cyanocinnamate (1 mumol/l) failed to reduce the BK-induced dilation. However, the H2O2 scavenger catalase (400 U/ml) abolished the response (from 54 +/- 11 to 0 +/- 2 mum; P < 0.01). The ATP-dependent K+ (K-ATP) channel inhibitor glibenclamide (10 mu mol/l) had a similar effect as well (from 54 +/- 11 to 16 +/- 5 mu m; P < 0.05). Coapplication of the Ca2+-dependent K+ channel inhibitors charybdotoxin (0.1 mumol/l) and apamin (0.5 mumol/l) failed to reduce the response. We conclude that H2O2 mediates the non-nitric oxide-, non-prostanoid-dependent vasorelaxation to BK in the piglet pial vasculature. The response is mediated via BK2 receptors and the opening of K-ATP channels.