Interrogating the Angiotensin Peptidome in Rodent Models of Illness and Disease
Kristen C. Smith1 and Stanley V. Smith2
1Mississippi INBRE Research Scholar, Tougaloo College, Tougaloo, MS
2Department of Pharmacology and Toxicology, The University of Mississippi Medical Center, Jackson, MS
Angiotensin II (Ang II) is a regulatory peptide hormone that is essential in regulating blood pressure and fluid balance. Ang II binds to and activates the AT1 receptor through a signal transduction pathway resulting in vasoconstriction, trophic and fibrotic effects, sodium reabsorption, and inflammation. Human diseases such as hypertension, diabetes, and chronic kidney disease can be caused or exacerbated by excessive levels of Ang II. In contrast, other Angiotensin I-derived peptides serve different functions. For example, Ang 1-7 causes vasodilation; is anti-inflammatory, and has several other beneficial effects. The levels of Ang II, Ang 1-7 and other Angiotensin-derived peptides are difficult to measure in plasma for a number of reasons including low abundance, contaminating peptides/proteins, and instability. This makes the Angiotensin Peptidome very difficult to quantify. We used Liquid Chromatography/Mass Spectrometry (LC/MS) to characterize the Angiotensin Peptidome of plasma samples from an acute kidney injury rodent model. Our results suggest that even though levels of the Ang I-derived peptides are very low, LC/MS provides the sensitivity to quantify the Angiotensin Peptidome. Preliminary results indicated that acute kidney injury results in elevated levels of Ang II while levels of Ang 1-7 are not significantly different in the injury state compared to controls. These experiments provide “proof in principle” that by utilizing plasma samples from rodent models of illness and disease, we can quantify differences in the Angiotensin Peptidome and that these differences will suggest pathways to target in order to predict disease state and evaluate the success of different drug treatment therapies.