Knockdown of adenosine receptors (A1 e A2a) in vivo and its influence on adenosine receptor dimerization and over the neuronal nitric oxide synthase in normotensive and hypertensive rats

• Grant number: 14/01024-3
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2015
• End date: January 31, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Debora Rejane Fior Chadi
• Grantee: Debora Rejane Fior Chadi
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Adenosine is part of a group of substances that act as endogenous modulators, involved in the regulation of physiological activity in many organs and tissues. Currently, this substance is extensively studied for therapeutic purposes, specifically those related to cardiovascular control.It is known that the nucleus of the solitary tract (NTS) is one of the most important neural centers related to cardiovascular control mediating instant adjustments of heart rate and blood pressure in various behavioral situations, thus in maintaining body homeostasis.Adenosine, within the NTS, acts as a potent modulator of hemodynamic activity of the sympathetic nervous system. The activation of its receptors directly influences the action of other neurotransmitters and receptors, exhibiting a powerful modulatory action on cardiovascular control. It is also known that adenosine receptors are increased in the NTS of spontaneously hypertensive rats (SHR), suggesting a role of this nucleoside on the genesis of hypertension.Nitric oxide (NO) also plays an important role in cardiovascular control within the NTS by acting as a hypotensive agent. It is also known that NO synthesis is altered in the NTS of SHR, suggesting an important contribution of this molecule on blood pressure control and the development of hypertension.The relationship between NO and adenosine in the peripheral system is already well established in the literature. It is known that adenosine stimulates NO production. However, this interaction within the NTS is not well explored. In this sense, the goal of our work is to analyze in vivo the effect of knockdown of adenosine receptors, A1R and A2AR, on the mRNA and protein nitric oxide synthase (NOS) in normotensive (WKY) and hypertensive (SHR) rats through cellular techniques and molecular. (AU)