Mechanisms involved in the cardiovascular and hydroelectrolytic changes induced by central Angiotensin II and osmoreceptors in rats fed with a high-fat diet

• Grant number: 19/22767-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2020
• Effective date (End): July 31, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Débora Simões de Almeida Colombari
• Grantee: Jéssica Matheus de Sá
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 15/23467-7 - Experimental pathophysiology: role of central mechanisms of the cardiovascular and respiratory control changes induced by experimental hypertension and obesity, AP.TEM
• Associated scholarship(s): 22/00977-3 - Effect of acute optogenetic and chronic chemogenetic activation of AT1a receptors in paraventricular nucleus neurons on energy metabolism in high-fat diet animals, BE.EP.DR

Abstract

During obesity, there is an increase in the renin-angiotensin system (RAS) activity. Thus, a greater RAS activation, and the consequent increased levels of peripheral angiotensin II (ANG II), can activate forebrain areas of the central nervous system (CNS) free of the blood brain barrier located in the lamina terminalis, and rich in ANG II receptors, such as the subfornical organ (SFO). We hypothesize that the activation of AT1 subtype receptors in SFO by angiotensin II activates neural pathways that lead to an increase in sympathetic activity and vasopressin secretion, and consequently blood pressure during obesity. Another interaction that may be occurring is a potentiation in the pressor response to osmotic stimuli, such as 12-h water deprivation and intragastric administration of 2 M NaCl, which are not yet known. Previous data from our laboratory showed that although the pressor response to ANG II has been potentiated, the same was not true for the dipsogenic effects of ANG II, perhaps due to the pressor effect of ANG II. Thus, we will also study whether animals fed with high-fat diet (HFD) have a 12-h water-induced change in water intake or 2 M NaCl gavage. These two osmotic stimuli do not cause major cardiovascular changes in control rats. However, we do not know whether in rats fed with HFD will be a potentiation or even a reduction in these responses. Changes in urinary excretion will also be evaluated in these animals. Finally, inflammatory cytokines are known to inhibit water intake and increase blood pressure. We will verify if there is interaction between central angiotensinergic and osmotic mechanisms with neuroinflammation in rats fed with HFD. Holtzman rats weighing between 300-320 g will be fed for 6 weeks with standard diet - standard rodent diet (11% of calories from fat) or palatable HFD (46% of calories from fat). Acute and chronic (telemetry) recording of blood pressure, water intake and urinary excretion, tissue collection for verification of gene expression and immunohistochemical labeling will be performed simultaneously to identify RAS genes in specific cells such as cytokine receptors and co-labelling of Fos (neuronal activation marker) and cytokines after osmotic stimulus in the lamina terminalis. (AU)