Opposing actions of angiotensin-(1-7) and angiotensin II in the brain of transgenic hypertensive rats.
Opposing actions of angiotensin-(1-7) and angiotensin II in the brain of transgenic hypertensive rats.
复制标题
血管紧张素-(1-7) 和血管紧张素 II 在转基因高血压大鼠脑中的相反作用。
DOI：
10.1161/01.hyp.25.6.1260
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Ferrario,CM
中科院分区：
文献类型：
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作者：
Moriguchi,A;Tallant,EA;Matsumura,K;Reilly,TM;Walton,H;Ganten,D;Ferrario,CM
由于缺乏氨基末端七肽血管紧张素-(1-7) [Ang-(1-7)] 的特异性拮抗剂，促使我们评估递送特异性亲和纯化的 Ang-(1-7) 抗体对表达小鼠颌下Ren-2d 基因 [(mRen-2d)27] 的 12 周龄有意识纯合雌性大鼠 (n=12) 的血压和心率的中心影响。基因组。另一组转基因高血压和菌株匹配的 Sprague-Dawley 对照被注射了特定的 Ang II 单克隆抗体 (KAA8)。在有意识的转基因高血压大鼠中，脑室给予亲和纯化的 Ang-(1-7) 抗体，可引起与心动过速相关的血压显着的剂量相关升高。在停止赖诺普利治疗后 7 至 10 天，转基因大鼠的高血压反应增强。用 Ang II 抗体中和 Ang II 引起与用 Ang-(1-7) 抗体获得的血流动力学反应相反的血流动力学反应。所有剂量的 Ang II 抗体都会产生低血压和心动过缓。在停止赖诺普利治疗的转基因大鼠中，抑制反应的强度显着增强。相比之下，中央给予Ang-(1-7)或Ang II抗体对血压正常的大鼠没有影响。中心注射亲和纯化的 IgG 组分对对照大鼠和转基因阳性大鼠均无效。这些数据表明，在转基因高血压大鼠的大脑中，Ang-(1-7)对抗Ang II对有助于维持这种高血压模型的一个或多个中枢机制的作用。此外，这些研究表明大脑肾素-血管紧张素系统对维持这种形式的单基因高血压有重要贡献。
Lack of specific antagonists to the amino-terminal heptapeptide angiotensin-(1-7) [Ang-(1-7)] prompted us to evaluate the central effects of delivering a specific affinity-purified Ang-(1-7) antibody on the blood pressure and heart rate of 12-week-old conscious homozygous female rats (n=12) expressing the mouse submandibularRen-2dgene [(mRen-2d)27] in their genome. Another group of transgenic hypertensive and strain-matched Sprague-Dawley controls were injected with a specific Ang II monoclonal antibody (KAA8). Cerebroventricular administration of the affinity-purified Ang-(1-7) antibody in conscious transgenic hypertensive rats caused significant dose-related elevations in blood pressure associated with tachycardia. The hypertensive response was augmented in transgenic rats studied 7 to 10 days after cessation of lisinopril therapy. Neutralization of Ang II with the Ang II antibody caused a hemodynamic response opposite to that obtained with the Ang-(1-7) antibody. All doses of the Ang II antibody produced hypotension and bradycardia. The magnitude of the depressor response was significantly augmented in transgenic rats weaned off lisinopril therapy. In contrast, central administration of either the Ang-(1-7) or Ang II antibodies had no effect on normotensive rats. Central injections of an affinity-purified IgG fraction were ineffective in both control and transgene-positive rats. These data suggest that in the brain of transgenic hypertensive rats, Ang-(1-7) opposes the action of Ang II on the central mechanism or mechanisms that contribute to the maintenance of this model of hypertension. In addition, these studies showed an important contribution of the brain renin-angiotensin system to the maintenance of this form of monogenetic hypertension.