Dysregulation of AT 1 receptor Signaling in the (mRen2)27 Transgenic Rat

Grant Winners

  • Michelle Clark, Ph.D. – College of Pharmacy
  • Ana Maria Castejon, Ph.D. – College of Pharmacy

Dean

  • William Hardigan – College of Pharmacy

Abstract

2004 Faculty Research and Development Grant Award Winner.

Hypertension is a major health problem in the United States where more than 50 million people have the condition. Chronic hypertension can lead to vital organ damage and contributes to more than 500,000 deaths in the United States annually. Angiotensin II (Ang II) is a biologically active octapeptide that triggers a myriad of physiological responses that may lead to hypertension. This project will use a hypertensive rat model known as the mRen2(27) transgenic rats to look at the effects of Ang II on hypertension. These hypertensive rats have overexpression of a gene for one of the proteins implicated in blood pressure regulation -renin. There is also a chronic increase in Ang II in their brain and blood vessels that ultimately results in an elevation of blood pressure. Astrocytes will be isolated from the brains of normotensive and hypertensive rats and studies outlined in this proposal will: (a) identify intracellular mechanisms responsible for dysregulation of the Ang II receptor in the transgenic rat by studying the regulation of the SAPK/JNK pathway and; (b) determine the molecular consequences of this Ang II receptor dysregulation in the transgenic rat by studying the regulation of c-jun, ATF-2 and elk-1 expression in these animals. The studies proposed are designed to determine whether effects of chronic elevation in Ang II may be overcome. Further, since in most cases the underlying cause of hypertension is not known, understanding how different types of cells are affected by long-term exposure to angiotensin molecules and how they, in turn, regulate blood pressure will allow us to design better drugs for the prevention and treatment of hypertension.