Brain renin-angiotensin system: effects of sinoaortic denervation and exercise in hypertensive rats

• Grant number: 18/12280-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2018
• Effective date (End): October 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Lisete Compagno Michelini
• Grantee: Louisi Almeida Manica
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Work of our group and others have indicated that the establishment of arterial hypertension is accompanied by autonomic dysfunction and hyperactivity of the Renin Angiotensin System (RAS) in the brain tissue. They also indicated that elevated levels of Angiotensin II (Ang II) contribute to sympathetic hypertonia, which in turn perpetuates hypertension, and that the reduction of blood pressure (BP) values was associated with RAS blockade. In previous work, we also demonstrated that low to moderate intensity aerobic training (T) in spontaneously hypertensive rats (SHR) reduces RAS activity in autonomic areas, increases baroreceptor reflex gain, reduces peripheral sympathetic activity, PA and heart rate (HR) and that these effects were blocked by sinoaortic denervation (SAD, Ceroni et al, 2009). We also demonstrated that SAD reduced the tone of pre-autonomic neurons of the Paraventricular Nucleus of the Hypothalamus (PVN), suggesting the importance of peripheral activity induced by exercise and carried by baroreceptors and peripheral chemoreceptors in reducing sympathetic activity. We do not know whether the activity of these receptors could also interfere with the expression of cerebral RAS, an important conditioner of sympathetic hypertonia in RHS. In order to identify the possible involvement of RAS in the genesis of these responses, we will evaluate the effects of SAD and T on baseline hemodynamics, baroreceptor reflex sensitivity, Angiotensinogen protein expression (Aogen), Angiotensin Converting Enzyme (ACE), Angiotensin 2 Converting Enzyme (ECA 2) and expression of AT1 and MAS receptors in PVN. SHR patients submitted to SAD or Sham surgery will be submitted to T protocols (50-60% of maximum physical capacity, 1h/day, 5 days / week) or sedentary lifestyle (S) for 8 weeks. At the end of the protocols, it will be cannulated to record baseline PA and HR, followed by confirmation of DSA by i.v infusion of vasoactive drugs (phenylephrine and sodium nitroprusside). The animals will be anesthetized for perfusion, fixation and removal of the brain, which will be post fixed and stored until the immunohistochemical processing for quantification of the different components of the RAS.