Effects of Angiotensin II receptor activation in endothelial cells and vascular smooth muscle cells of 2K1C rats

• Grant number: 16/20322-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2017
• End date: October 31, 2020
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Lusiane Maria Bendhack
• Grantee: Bernah Mathias Fahning
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The 2K-1C renal hypertension model is characterized by activation of the renin-angiotensin-aldosterone system (RAAS). Angiotensin II (Ang II) is the main peptide of RAAS that promotes vascular smooth muscle cells contraction by AT1 receptor activation. AT1 is expressed in endothelial cells and is involved in NADPH-oxidase (NOX) activation, increased production of reactive oxygen species (ROS) and reduced bioavailability of nitric oxide (NO). The RAAS is activated in the 2K-1C model, which causes endothelial dysfunction due to the sustained activation of RAAS downstream signaling pathways. In addition to RAAS, ROS can also be produced by the endothelial NOX, NO synthase (eNOS), and cyclooxygenase (COX), which highlights that both NOS and COX share similar signaling pathways. It is known that NO production can stimulate the production of COX signaling pathway mediators, and NO and prostaglandins (PGs) interaction is not unidirectional since PGs are able to reduce NOS activity. However, the exact mechanism by which NO modulates PGs production, and vice versa, is still controversial. This study aims to assess the RAAS interaction with NO and COX signaling pathways. Our hypothesis is that in 2K-1C aorta, AT1 receptors activated by Ang II in the endothelial cells modulate the endothelial COX activity by the increased ROS production via uncloupled eNOS and reduced NO bioavailability. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FAHNING, Bernah Mathias. Effects of angiotensin II receptor activation on endothelial cells and vascular smooth muscle cells in renal hypertensive rat aortas. 2021. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.