Angiotensin-(1-7) Central Mechanisms After ICV Infusion in Hypertensive Transgenic (mRen2)27 Rats

Lucas M Kangussu; Marcella Nunes Melo-Braga; Bruna Soares de Souza Lima; Robson A S Santos; Hélida Monteiro de Andrade; Maria José Campagnole-Santos

doi:10.3389/fnins.2021.624249

Angiotensin-(1-7) Central Mechanisms After ICV Infusion in Hypertensive Transgenic (mRen2)27 Rats

Front Neurosci. 2021 Apr 23:15:624249. doi: 10.3389/fnins.2021.624249. eCollection 2021.

Authors

Lucas M Kangussu^{1

2}, Marcella Nunes Melo-Braga³, Bruna Soares de Souza Lima⁴, Robson A S Santos^{1

5}, Hélida Monteiro de Andrade⁴, Maria José Campagnole-Santos^{1

5}

Affiliations

¹ National Institute of Science and Technology in Nanobiopharmaceutics (INCT-Nanobiofar), Federal University of Minas Gerais, Belo Horizonte, Brazil.
² Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
³ Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
⁴ Department of Parasitology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
⁵ Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Abstract

Previous data showed hypertensive rats subjected to chronic intracerebroventricular (ICV) infusion of angiotensin-(1-7) presented attenuation of arterial hypertension, improvement of baroreflex sensitivity, restoration of cardiac autonomic balance and a shift of cardiac renin-angiotensin system (RAS) balance toward Ang-(1-7)/Mas receptor. In the present study, we investigated putative central mechanisms related to the antihypertensive effect induced by ICV Ang-(1-7), including inflammatory mediators and the expression/activity of the RAS components in hypertensive rats. Furthermore, we performed a proteomic analysis to evaluate differentially regulated proteins in the hypothalamus of these animals. For this, Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats (TG) were subjected to 14 days of ICV infusion with Ang-(1-7) (200 ng/h) or 0.9% sterile saline (0.5 μl/h) through osmotic mini-pumps. We observed that Ang-(1-7) treatment modulated inflammatory cytokines by decreasing TNF-α levels while increasing the anti-inflammatory IL-10. Moreover, we showed a reduction in ACE activity and gene expression of AT1 receptor and iNOS. Finally, our proteomic evaluation suggested an anti-inflammatory mechanism of Ang-(1-7) toward the ROS modulators Uchl1 and Prdx1.

Keywords: ROS modulators; angiotensin-(1-7); cytokines; hypertensive transgenic (mRen2)27 rats; hypothalamus; iNOS.