Investigation and Characterization of Metabolic Rates of Angiotensin II and Associated Bioactive Derivatives in the Renin-Angiotensin System

Investigation and Characterization of Metabolic Rates of Angiotensin II and Associated Bioactive Derivatives in the Renin-Angiotensin System

To maintain homeostasis, the renin-angiotensin system (RAS) works to regulate the cardiovascular, renal, respiratory, and neurological systems of the body through activation of both the vasoconstrictive and proliferative arm of ACE/Ang II/AT1R and the vasodilative and antiproliferative arm of ACE- 2/Ang(1-7)/Mas axis. To better understand their interaction, the components of the alternate RAS and the classical RAS in the homeostatic systems of the body are researched and analyzed. One of the significant constituents of the classical pathway is the octapeptide hormone angiotensin II (Ang II). It is a major contributor to vasoconstriction and peripheral vascular resistance through the activation of AT1R especially with its large amount of associated bioactive peptides such as Ang III (angiotensin-(2- 8)), the less common Ang IV (angiotensin-(3-8)), and Ang V (angiotensin-(4-8)). The project aims to highlight the metabolism of Ang II and its derivatives, which were extracted from blood of Wistar rats, separated by paper chromatography, and measured by high performance liquid chromatography (HPLC) while in the presence of various concentrations of ACE-2. The results are among the first of numerous studies to measure and compare the rate of enzymatic activity of ACE-2 in the conversion of Ang II metabolites to a more active conformation state that plays a beneficial role in the alternative axis of the RAS. These results would essentially allow for optimization of new treatments through control of angiotensinase activity to prevent the onset of diseases caused by the overexpression of the classical axis of the RAS.