Kohagura K, Endo Y, Ito O, Arima S, Omata K, Ito S
The Second Department of Internal Medicine, Tohoku University School of Medicine, 1-1, Seiryo-cho, Aoba-ku, Sendai, Japan.
Acta Physiol Scand. 2000 Jan;168(1):107-12. doi: 10.1046/j.1365-201X.2000.00638.x.
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 NG-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.
一氧化氮（NO）和环氧二十碳三烯酸（EETs）是花生四烯酸的细胞色素P450环氧化酶代谢产物，由血管内皮释放，在肾小球血流动力学控制中发挥重要作用。我们研究了内源性NO或EETs是否调节兔肾分离的微灌注入球小动脉（Af-Art）中血管紧张素II（AngII）诱导的收缩。当用NG-硝基-L-精氨酸甲酯（L-NAME，一种NO合成抑制剂；10-4 mol/L）或咪康唑（一种P450环氧化酶抑制剂；10-6 mol/L）处理Af-Arts时，基础直径分别降低了34.5±2.2%和13.9±3.2%。添加到浴槽和管腔中的AngII以剂量依赖性方式降低了Af-Arts的直径。用L-NAME或咪康唑预处理也增强了对AngII的收缩反应。在对照组、L-NAME处理组和咪康唑处理组中，10-8 mol/L的AngII分别将直径降低至39.2±1.4%、32.9±3.6%和12.7±4.6%。为了研究血管紧张素II 2型（AT2）受体是否通过NO或EETs调节AngII的作用，我们在存在PD123319（一种AT2受体拮抗剂；10-7 mol/L）的情况下重复了实验。在存在PD123319的情况下，L-NAME仍然增强了对AngII的收缩反应，然而，咪康唑没有作用。在存在PD123319的情况下，10-8 mol/L的AngII在对照组、L-NAME处理组和咪康唑处理组中分别将直径降低至25.0±4.6%、9.4±4.0%和26.0±3.3%。这些结果表明：（1）NO和EETs的张力性释放减弱了Af-Arts对AngII的血管收缩反应；（2）AT2受体似乎与EETs而非NO途径偶联。
