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The role of the purinergic receptors at the paraventricular nucleus of the hypothalamus on the salt-induced hypertension

Grant number: 16/19162-9
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2016
Effective date (End): November 30, 2017
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Vagner Roberto Antunes
Grantee:Johnny Mendes Mendonça
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Hypertension is among the diseases that most affect the people around the world, causing high mortality rate. According to the World Health Organization (WHO), one in three people had their blood pressure increased to high levels, and this has been the cause of nearly half of all deaths from stroke and cardiovascular disease. Hypertension is a polygenic and multifactorial disease, and bad eating habits and lifestyle also influence the blood pressure levels, including high salt diets. High salt intake causes rise in the plasma osmolality (hyperosmolality), increasing blood volume and arterial pressure. Plasma hyperosmolality is detected by central osmoreceptors located at the brain level called circumventricular organs (CVOs), which maintains direct connections with different nuclei of the central nervous system (CNS), including the paraventricular nucleus of the hypothalamus (PVN), a brain area that is directly related to the control of the autonomic nervous system (ANS). Several studies support the hypothesis that increase in the plasma osmolality increase the sympathetic nervous system via excitation of the PVN neurons that have inputs with others brainstem nuclei as part of the autonomic nervous system, such as RVLM and CILM. Recent studies from our laboratory have demonstrated the important role of purinergic signaling, specifically adenosine triphosphate (ATP), acting in the PVN in control of sympathetic activity. In addition to the role of ATP as a neurotransmitter, there is also strong evidence that it can act as co-transmitter in different physiological conditions. Despite these results still remaining a question about the physiological role of purines (ATP and adenosine) at PVN neurons in a condition of salt-induced hypertension. Thus, our hypothesis is that the purinergic neurotransmission in PVN neurons play a significant role in the modulation of sympathetic hyperactivation induced by salt loading. Therefore, the aim of this project is to evaluate whether the salt-induced hypertension would be affected by the antagonism of purinergic receptors ATP and adenosine in the paraventricular nucleus of the hypothalamus to non-anesthetized animals. (AU)

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