Endogenous nitric oxide and epoxyeicosatrienoic acids modulate angiotensin II-induced constriction in the rabbit afferent arteriole
Endogenous nitric oxide and epoxyeicosatrienoic acids modulate angiotensin II-induced constriction in the rabbit afferent arteriole
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DOI：
10.1046/j.1365-201x.2000.00638.x
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Ito, S
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文献类型：
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作者：
Kohagura, K;Endo, Y;Ito, S
一氧化氮 (NO) 和环氧二十碳三烯酸 (EET) 是花生四烯酸的细胞色素 P450 环氧化酶代谢物，由血管内皮释放，在控制肾小球血流动力学中发挥重要作用。我们检查了内源性 NO 或 EET 是否调节血管紧张素 II-(AngII) 诱导的兔肾微灌注传入小动脉 (Af-Art) 收缩。当Af-Arts用N-G-硝基-L-精氨酸甲酯（L-NAME，NO合成抑制剂；10(-4) mol L-1）或咪康唑（P450环氧化酶抑制剂；10(-6) mol L-1）处理时，基底直径分别减少了34.5 +/- 2.2和13.9 +/- 3.2%。添加到浴和管腔中的 AngII 以剂量依赖性方式减小了 Af-Arts 的直径。用 L-NAME 或咪康唑进行预处理也增强了大蟒蛇对 AngII 的反应。在对照组、L-NAME治疗组和咪康唑治疗组中，10(-8) mol L-1 AngII将直径分别减小至39.2 +/- 1.4、32.9 +/- 3.6和12.7 +/- 4.6%。为了研究AngII 2 型(AT2) 受体是否通过NO 或EET 调节AngII 作用，我们在PD123319（一种AT2 受体拮抗剂；10(-7) mol L-1）存在下重复了实验。在存在 PD123319 的情况下，L-NAME 仍然增强了收缩器对 AngII 的反应，但咪康唑没有效果。在PD123319存在的情况下，在对照组、L-NAME治疗组和咪康唑治疗组中，10(-8) mol L-1的AngII将直径分别减小至25.0 +/- 4.6、9.4 +/- 4.0和26.0 +/- 3.3%。这些结果表明，(1) NO 和 EET 的强直释放减弱了 Af-Arts 中对 AngII 的血管收缩反应，(2) AT2 受体似乎与 EET 偶联，而不是与 NO 途径偶联。
Nitric oxide (NO) and epoxyeicosatrienoic acids (EETs), cytochrome P450 epoxygenase metabolites of arachidonic acid, are released by the vascular endothelium and play important roles in the control of glomerular haemodynamics. We examined whether endogenous NO or EETs modulate angiotensin II- (AngII) induced constriction in isolated microperfused afferent arteriole (Af-Art) of the rabbit kidney. When Af-Arts were treated with N-G-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthese; 10(-4) mol L-1) or miconazole (an inhibitor of P450 epoxygenase; 10(-6) mol L-1), basal diameter was decreased by 34.5 +/- 2.2 and 13.9 +/- 3.2%, respectively. AngII added to both the bath and lumen decreased the diameter of Af-Arts in a dose-dependent manner. Pretreatment with either L-NAME or miconazole also augmented the constrictor response to AngII. AngII at 10(-8) mol L-1 decreased the diameter to 39.2 +/- 1.4, 32.9 +/- 3.6, and 12.7 +/- 4.6%, in control, L-NAME-, and miconazole-treated group, respectively. In order to study whether the AngII type2 (AT2) receptor modulates AngII action via NO or EETs, we repeated the experiments in the presence of PD123319 (an AT2 receptor antagonist; 10(-7) mol L-1). In the presence of PD123319, L-NAME still augmented the constrictor response to AngII, however, miconazole had no effect. In the presence of PD123319, AngII at 10(-8) mol L-1 decreased the diameter to 25.0 +/- 4.6, 9.4 +/- 4.0, and 26.0 +/- 3.3%, in control, L-NAME-, and miconazole-treated group, respectively. These results suggest that (1) tonic release of NO and EETs attenuates the vasoconstrictor response to AngII in Af-Arts and (2) AT2 receptor seems to be coupled to EETs rather than the NO pathway.