Tamura M, Takagi T, Howard E F, Landon E J, Steimle A, Tanner M, Myers P R
Department of Biochemistry, Vanderbilt University School of Medicine and Veterans Affairs Medical Center, Nashville, Tennessee 37232, USA.
J Hypertens. 2000 Sep;18(9):1239-46. doi: 10.1097/00004872-200018090-00010.
Chronic feeding of a purified synthetic diet induces renin-angiotensin system-dependent moderate high blood pressure in normal Sprague-Dawley rats. The present study was designed to characterize the angiotensin II (Ang II) receptor type 2 (AT2)-specific mechanism of blood pressure regulation in these rats.
The effect of the AT2 receptor antagonist PD123319 (PD) on blood pressure was examined in vivo in synthetic diet-fed rats. Ang II-dependent contraction of aortic rings prepared from the synthetic diet-fed rats was also investigated.
After 8 weeks of feeding the synthetic diet, the mean arterial pressure (MAP) was significantly elevated above levels measured in control rats (117 +/- 2 versus 102 +/- 3 mmHg, P < 0.05). Intravenous administration of PD to conscious hypertensive rats elicited an immediate dose-dependent increase in MAP that was sustained for approximately 7.4 min with 3 mg/kg PD. The angiotensin converting enzyme inhibitor captopril, but not the Ang II type 1 receptor blocker losartan, significantly attenuated the effect of PD on blood pressure. PD did not increase the plasma level of catecholamines. The PD-dependent blood pressure increase was not observed in normotensive control rats. Aortic ring assays revealed that functional activation of the AT2 receptor occurs only in the hypertensive rats, and this AT2 response is abolished by indomethacin (5 micromol/l) but not by Nomega-nitro-L-arginine methyl ester (100 Fmol/l).
These results clearly demonstrate that AT2 receptor-mediated blood pressure regulation is functional in this experimental model of hypertension. Furthermore, cyclooxygenase metabolites might be the key mediators for the AT2 receptor-mediated blood pressure-lowering action.
长期给正常的斯普拉格-道利大鼠喂食纯化的合成饮食会诱导肾素-血管紧张素系统依赖性中度高血压。本研究旨在阐明这些大鼠中血管紧张素 II（Ang II）2 型受体（AT2）特异性的血压调节机制。
在喂食合成饮食的大鼠体内检测 AT2 受体拮抗剂 PD123319（PD）对血压的影响。还研究了从喂食合成饮食的大鼠制备的主动脉环的 Ang II 依赖性收缩。
喂食合成饮食 8 周后，平均动脉压（MAP）显著高于对照大鼠测量的水平（117±2 与 102±3 mmHg，P<0.05）。给清醒的高血压大鼠静脉注射 PD 会引起 MAP立即出现剂量依赖性升高，3 mg/kg PD 时这种升高持续约 7.4 分钟。血管紧张素转换酶抑制剂卡托普利可显著减弱 PD 对血压的影响，而 Ang II 1 型受体阻滞剂氯沙坦则无此作用。PD 不会增加儿茶酚胺的血浆水平。在血压正常的对照大鼠中未观察到 PD 依赖性血压升高。主动脉环实验表明，AT2 受体的功能激活仅发生在高血压大鼠中，吲哚美辛（5 μmol/l）可消除这种 AT2 反应，而 Nω-硝基-L-精氨酸甲酯（100 μmol/l）则不能。
这些结果清楚地表明，AT2 受体介导的血压调节在该高血压实验模型中起作用。此外，环氧化酶代谢产物可能是 AT2 受体介导的降压作用的关键介质。
