Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
Am J Med Sci. 2010 Jun;339(6):543-8. doi: 10.1097/MAJ.0b013e3181d82a62.
Transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)] allow induction of various degrees of ANG II-dependent hypertension. Dietary administration of the aryl hydrocarbon indole-3-carbinol (I3C) at a dose of 0.15% induces a slowly developing form of ANG II-dependent hypertension, whereas dietary administration of a higher dose (0.3%) of I3C results in the development of ANG II-dependent malignant hypertension. Cessation of administration of 0.15% I3C results in the normalization of blood pressure, indicating the reversibility of hypertension induced by this dose of I3C. The present study was performed to determine if ANG II-dependent malignant hypertension is similarly reversible following cessation of dietary administration of 0.3% I3C.
Cyp1a1-Ren2 rats (n = 6) were fed a normal diet containing 0.3% I3C for 11 days to induce malignant hypertension.
Cyp1a1-Ren2 rats induced with I3C exhibited pronounced increases in systolic blood pressure (SBP) (132 +/- 3-229 +/- 11 mm Hg, P < 0.001) and marked decreases in body weight (303 +/- 4-222 +/- 2 g, P < 0.001). When I3C administration was terminated, SBP decreased to 167 +/- 4 mm Hg (P < 0.01) and body weight increased to normal levels (309 +/- 2 g, P < 0.01) within 12 days. However, SBP remained significantly elevated (172 +/- 1 mm Hg, P < 0.01) for up to 3 weeks after termination of dietary administration of 0.3% I3C. In addition, the magnitude of the blood pressure response to intravenous bolus administration of 50 ng of ANG II (50 microL in volume) 3 weeks after cessation of dietary I3C administration was substantially higher than that observed in normotensive control rats (134 +/- 1 mm Hg, n = 6) not previously induced with 0.3% I3C (53 +/- 2 versus 38 +/- 3 mm Hg, P < 0.05).
The present findings demonstrate that transient induction of ANG II-dependent malignant hypertension results in prolonged elevations of arterial blood pressure and marked augmentation of the magnitude of the pressor response to ANG II in Cyp1a1-Ren2 transgenic rats.
具有诱导表达小鼠 Ren2 肾素基因的转基因大鼠[品系名称：TGR（Cyp1a1Ren2）]允许诱导各种程度的 ANG II 依赖性高血压。饮食给予 0.15%的芳香烃吲哚-3-卡宾醇（I3C）可诱导出一种缓慢发展的 ANG II 依赖性高血压，而饮食给予更高剂量（0.3%）的 I3C 会导致 ANG II 依赖性恶性高血压的发展。停止给予 0.15%的 I3C 会导致血压正常化，表明该剂量的 I3C 诱导的高血压是可逆的。本研究旨在确定在停止饮食给予 0.3%的 I3C 后，ANG II 依赖性恶性高血压是否同样可逆。
Cyp1a1-Ren2 大鼠（n=6）喂食含有 0.3%I3C 的正常饮食 11 天以诱导恶性高血压。
用 I3C 诱导的 Cyp1a1-Ren2 大鼠的收缩压（SBP）显著升高（132 +/- 3-229 +/- 11mmHg，P < 0.001），体重明显下降（303 +/- 4-222 +/- 2g，P < 0.001）。当 I3C 给药停止时，SBP 下降至 167 +/- 4mmHg（P < 0.01），体重增加至正常水平（309 +/- 2g，P < 0.01），在 12 天内。然而，在停止饮食给予 0.3%I3C 后长达 3 周，SBP 仍显著升高（172 +/- 1mmHg，P < 0.01）。此外，在停止饮食给予 0.3%I3C 3 周后，静脉注射 50ng ANG II（体积 50μL）时的血压反应幅度明显高于未用 0.3%I3C 预先诱导的正常血压对照大鼠（134 +/- 1mmHg，n=6）（53 +/- 2 与 38 +/- 3mmHg，P < 0.05）。
本研究结果表明，短暂诱导 ANG II 依赖性恶性高血压会导致动脉血压持续升高，并显著增强 Cyp1a1-Ren2 转基因大鼠对 ANG II 的升压反应幅度。
