Physiological characterization of the hypertensive transgenic rat TGR(mREN2)27

Abstract

Transgenic techniques represent powerful tools for the study of gene-related mechanisms of diseases such as hypertension, which results from a complex interaction between genetic and environmental factors. The renin-angiotensin system, a biochemical cascade in which renin functions as the key enzyme in the formation of the effector peptide angiotensin II, plays a major role in the regulation of blood pressure. The renin gene, therefore, represents an important candidate gene for hypertension. Because rats are more suited than mice for a number of experimental settings often employed in cardiovascular research, we modified the transgenic technique to generate the transgenic rat strain TGR(mREN2)27 harboring the murine Ren-2 gene. These transgenic rats develop fulminant hypertension at an early age despite low levels of renin in plasma and kidney. In addition, high expression of the transgene in a number of extrarenal tissues is associated with increased local formation of angiotensin II. Thus the TGR(mREN2)27 rat represents a model of hypertension with a defined genetic background. Studies on the transgenic rat may not only provide new insights into pathophysiological mechanisms of hypertension in this animal model but also offer the unique possibility to investigate the function and regulation of renin-angiotensin systems in extrarenal tissues. The aim of this review is to compile the knowledge that has been accumulated to date on this transgenic rat and to discuss possible mechanisms responsible for its hypertensive phenotype.