Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, CEP: 31.270.100, Belo Horizonte, Brazil.
Eur J Pharmacol. 2013 Aug 5;713(1-3):1-5. doi: 10.1016/j.ejphar.2013.04.032. Epub 2013 May 9.
Angiotensin II (Ang II) may be produced directly from angiotensinogen by tonin. Studies have demonstrated that Ang II and its metabolite Ang-(1-7) produce antinociception in pain animal models. The aim of the present study was to determine whether the transgenic mice that express rat tonin (TGM(rTon)) show altered nociceptive behavior and investigate the possible involvement of angiotensin metabolites. Nociception was evaluated using the thermal tail-flick and chemical acetic acid writhing tests, and the drugs were administered by intracerebroventricular and subcutaneous pathways, respectively. Probabilities less than 5% (P<0.05) were considered to be statistically significant (t test; ANOVA/Bonferroni's test). The results demonstrate that the transgenic mice showed an antinociceptive effect in the tail-flick and acetic acid writhing tests. In addition, it was observed that losartan, an AT₁ receptor antagonist and A-779 (D-Ala7-Ang-(1-7)), a Mas receptor antagonist attenuated the antinociceptive behavior. Our data suggest that the Ang II produced in TGM(rTon) induces antinociception via the AT₁ receptor, while the Ang-(1-7) produced from Ang II induced antinociception via the Mas receptor.
血管紧张素 II（Ang II）可能通过紧张素原直接产生。研究表明，Ang II 及其代谢产物 Ang-(1-7)在疼痛动物模型中产生镇痛作用。本研究旨在确定表达大鼠紧张素（TGM(rTon))的转基因小鼠是否表现出改变的痛觉行为，并研究血管紧张素代谢物的可能参与。使用热尾闪烁和化学醋酸扭体试验评估痛觉，分别通过脑室内和皮下途径给予药物。概率小于 5%（P<0.05）被认为具有统计学意义（t 检验；ANOVA/Bonferroni 检验）。结果表明，转基因小鼠在尾闪烁和醋酸扭体试验中表现出镇痛作用。此外，观察到 AT₁ 受体拮抗剂洛沙坦和 Mas 受体拮抗剂 A-779（D-Ala7-Ang-(1-7)) 减弱了镇痛行为。我们的数据表明，TGM(rTon) 中产生的 Ang II 通过 AT₁ 受体诱导镇痛，而 Ang II 产生的 Ang-(1-7) 通过 Mas 受体诱导镇痛。
