Deans

Andrés Malavé, Ph.D. – College of Pharmacy Robert Uchin, D.D.S. – College of Dental Medicine

Award Date

1-1-2013

Abstract

Hypertension (increased blood pressure) is an insidious pathological condition that leads to numerous diseases. There are many antihypertensive medications available; however, the number of cases and deaths attributed to hypertension are increasing. At the core of these cases is that at least 90% of the causes of hypertension are unknown. Angiotensin II (Ang II) is a bioactive molecule (peptide) that is important in regulating blood pressure. Thus, many antihypertensive medications target the synthesis or mechanisms of actions of the peptide. In the brain, Ang II mediates blood pressure control, and its actions may be dysregulated in hypertension. In this study, we will use astrocytes (a type of brain cell) isolated from spontaneously hypertensive rats (SHR) and their normotensive controls (having normal blood pressure) to elucidate central Ang II pathways that may become dysregulated during hypertension. Ang II induces oxidative stress factors known as reactive oxygen species (ROS) leading to deleterious and beneficial effects. Imbalances between synthesis and degradation of ROS (primarily hydrogen peroxide, H2O2) has many biological consequences, such as - oxidative stress, increase in immune (inflammatory) substances such as Interleukin-6 (IL-6), hypertension, and other types of cardiovascular diseases. We hypothesize that in SHR, ROS, IL-6 protein and IL-6 gene expression (mRNA) levels may be differentially regulated by Ang II contributing to hypertension in these animals. In this study, we propose to: a) determine whether Ang II induces ROS (H2O2) production in astrocytes isolated from SHR; b) determine whether Ang II-induced IL-6 mRNA levels and IL-6 protein secretion are dysregulated in astrocytes isolated from SHR; and c) determine intracellular signals that mediate Ang II-induced ROS (H2O2) generation, IL-6 mRNA levels and IL-6 protein secretion. Understanding the pathophysiology of Ang II in hypertension is essential to allow us to better prevent and treat this disease.

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