Role of the AT1R in the commissural NTS on development of renovascular hypertension

• Grant number: 16/02091-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): August 01, 2016
• Effective date (End): February 28, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Eduardo Colombari
• Grantee: Mariana Del Rosso de Melo
• Supervisor: Andrew M. Allen
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Research place: University of Melbourne, Australia
• Associated to the scholarship: 14/01159-6 - Role of reactive oxygen species (ROS) within the NTS on development and maintenance of hypertension on 2 kidney-1 clip renovascular, BP.DR

Abstract

Renovascular hypertension affects 1 - 4% of the hypertensive population and it is the largest cause of secondary hypertension, affecting 25% to 35% of the patients with secondary hypertension. Renovascular hypertension is also called Goldblatt hypertension and is induced experimentally by unilateral stenosis of a renal artery, which decreases renal perfusion pressure leading to renin release. Renin-angiotensin system (RAS) overactivity is related to the development of many forms of human hypertension and, because of that, ANG II, the mainly active peptide of this system, has been the target of many studies. ANG II has a key role in the brain, modulating the release of vaso- and reno-active hormones from the neurohypophysis, stimulating water intake and regulating neural control of cardiovascular function. Thus, understanding the cardiovascular changes induced by ANG II in the brain might contribute to development of new treatments for renovascular hypertension. An important brain area involved in cardiovascular control is the nucleus of the solitary tract (NTS). The involvement of the NTS in cardiovascular regulation is well described. However, in exciting results from my PhD we have shown that neurons of commissural NTS (cNTS) are more activated in 2K1C rats and may contribute to the maintenance of hypertension in this model. The NTS contains a high density of receptors for Ang II and these receptors have a cardiovascular role on normotensive mice. My preliminary data shows that blocking activation of the type 1 receptor for Ang II (AT1R) in the cNTS decreases blood pressure more in 2K1C rats than in normotensive rats. This points to a role for Ang II and theAT1R in the cNTS in the maintenance of hypertension in renovascular hypertension. As a consequence it becomes very important to understand whether the AT1R in cNTS also plays a role in the development of renovascular hypertension - currently this is unknown. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MELO, MARIANA ROSSO; VOGER, JOSHUA J.; CONNELLY, ANGELA A.; BASSI, JASPREET K.; COLOMBARI, EDUARDO; ALLEN, ANDREW M.. Chemogenetic inhibition of Phox2-expressing neurons in the commissural NTS decreases blood pressure in anesthetized spontaneously hypertensive rats. Neuroscience Letters, v. 787, p. 6-pg., 2022-07-30. (15/23467-7, 16/02091-1, 14/01159-6, 13/17251-6)

DE MELO, MARIANA DEL ROSSO; ONG, SARAH J. M.; CONNELLY, ANGELA A.; BASSI, JASPREET K.; COLOMBARI, EDUARDO; ALLEN, ANDREW M.. Involvement of Phox2B Neurons Located in the Commissural NTs with the Maintenance of Hypertension in SH Rats. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (16/02091-1, 15/23467-7)