National Institute of Science and Technology in Nanobiopharmaceutics (INCT-Nanobiofar Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil;
Am J Physiol Heart Circ Physiol. 2013 Oct 1;305(7):H1057-67. doi: 10.1152/ajpheart.00433.2013. Epub 2013 Jul 19.
Recent data indicate the brain angiotensin-converting enzyme/ANG II/AT1 receptor axis enhances emotional stress responses. In this study, we investigated whether its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/ANG-(1-7)/Mas axis, attenuate the cardiovascular responses to acute emotional stress. In conscious male Wistar rats, the tachycardia induced by acute stress (air jet 10 l/min) was attenuated by intravenous injection of ANG-(1-7) [Δ heart rate (HR): saline 136 ± 22 vs. ANG-(1-7) 61 ± 25 beats/min; P < 0.05]. Peripheral injection of the ACE2 activator compound, XNT, abolished the tachycardia induced by acute stress. We found a similar effect after intracerebroventricular injections of either ANG-(1-7) or XNT. Under urethane anesthesia, the tachycardia evoked by the beta-adrenergic agonist was markedly reduced by ANG-(1-7) [ΔHR: saline 100 ± 16 vs. ANG-(1-7) 18 ± 15 beats/min; P < 0.05]. The increase in renal sympathetic nerve activity (RSNA) evoked by isoproterenol was also abolished after the treatment with ANG-(1-7) [ΔRSNA: saline 39% vs. ANG-(1-7) -23%; P < 0.05]. The tachycardia evoked by disinhibition of dorsomedial hypothalamus neurons, a key nucleus for the cardiovascular response to emotional stress, was reduced by ∼45% after intravenous injection of ANG-(1-7). In cardiomyocyte, the incubation with ANG-(1-7) (1 μM) markedly attenuated the increases in beating rate induced by isoproterenol. Our data show that activation of the ACE2/ANG-(1-7)/Mas axis attenuates stress-induced tachycardia. This effect might be either via the central nervous system reducing anxiety level and/or interfering with the positive chronotropy mediated by activation of cardiac β adrenergic receptors. Therefore, ANG-(1-7) might contribute to reduce the sympathetic load to the heart during situations of emotional stress, reducing the cardiovascular risk.
最近的数据表明，大脑血管紧张素转换酶/血管紧张素 II/AT1 受体轴增强了情绪应激反应。在这项研究中，我们研究了其反向调节轴，血管紧张素转换酶 2（ACE2）/血管紧张素-(1-7)/Mas 轴，是否会减轻急性情绪应激对心血管的反应。在清醒的雄性 Wistar 大鼠中，急性应激（空气喷射 10 l/min）引起的心动过速被静脉注射血管紧张素-(1-7)减弱[Δ心率（HR）：盐水 136±22 与血管紧张素-(1-7) 61±25 次/分；P<0.05]。外周注射 ACE2 激活剂化合物 XNT 可消除急性应激引起的心动过速。我们发现，无论是经脑室内注射血管紧张素-(1-7)还是 XNT，都有类似的效果。在氨基甲酸乙酯麻醉下，β-肾上腺素能激动剂引起的心动过速明显被血管紧张素-(1-7)减弱[ΔHR：盐水 100±16 与血管紧张素-(1-7) 18±15 次/分；P<0.05]。异丙肾上腺素引起的肾交感神经活动（RSNA）增加也被血管紧张素-(1-7)治疗后消除[ΔRSNA：盐水 39%与血管紧张素-(1-7) -23%；P<0.05]。静脉注射血管紧张素-(1-7)后，去抑制背内侧下丘脑神经元引起的心动过速减少了约 45%。在心肌细胞中，孵育 1 μM 的血管紧张素-(1-7)可显著减弱异丙肾上腺素引起的搏动率增加。我们的数据表明，激活 ACE2/血管紧张素-(1-7)/Mas 轴可减轻应激引起的心动过速。这种作用可能是通过中枢神经系统降低焦虑水平和/或通过干扰心脏β肾上腺素能受体激活引起的正变时性来实现的。因此，血管紧张素-(1-7)可能有助于在情绪应激时减少心脏的交感神经负荷，降低心血管风险。
