PHYSIOLOGICAL CHARACTERIZATION OF THE HYPERTENSIVE TRANSGENIC RAT TGR(MREN2)27

Transgenic techniques represent powerful tools for the study of gene-r elated 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 functio ns as the key enzyme in the formation of the effector peptide angioten sin II, plays a major role in the regulation of blood pressure. The re nin gene, therefore, represents an important candidate gene for hypert ension. Because rats are more suited than mice for a number of experim ental settings often employed in cardiovascular research, we modified the transgenic technique to generate the transgenic rat strain TGR(mRE N2)27 harboring the murine Ren-2 gene. These transgenic rats develop f ulminant hypertension at an early age despite low levels of renin in p lasma and kidney. In addition, high expression of the transgene in a n umber of extrarenal tissues is associated with increased local formati on of angiotensin II. Thus the TGR(mREN2)27 rat represents a model of hypertension with a defined genetic background. Studies on the transge nic rat may not only provide new insights into pathophysiological mech anisms of hypertension in this animal model but also offer the unique possibility to investigate the function and regulation of renin-angiot ensin systems in extrarenal tissues. The aim of this review is to comp ile the knowledge that has been accumulated to date on this transgenic rat and to discuss possible mechanisms responsible for its hypertensi ve phenotype.