• Augusto Martins Lima, Carlos Henrique Xavier, Anderson José Ferreira, Mohan K Raizada, Gerd Wallukat, Elizabeth Portugal Pimenta Velloso, Robson Augusto Sousa dos Santos, and Marco Antônio Peliky Fontes.
• 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.

AbstractRecent 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.

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