The renin-angiotensin system and renal function in transgenic (mRen2)27 rats

Abstract

The transgenic rat (TGR)(mRen2)27 was the first hypertensive transgenic rat model developed. The model is unique in that it allows studying the effects of a single gene, namely the mouse salivary gland renin gene (mRen2), in the rat. The transgene is expressed in various rat tissues, including the central nervous system, adrenal gland, and the kidney. TGR exhibit a rightward shifted pressure-natriuresis curve that is overwhelmingly angiotensin II (Ang II) dependent. The mRen2 transgene, the rat's own renin gene, angiotensinogen, and the type 1 Ang II receptor, AT1, are all expressed in the kidneys of TGR. The rat's own renin gene is regulated normally in renal tissue, while the mRen2 transgene operates independently of blood pressure. These results, coupled with findings that the mRen2 transgene product converts rat angiotensinogen more effectively than endogenous rat renin, that the TGR may have high circulating mouse renin levels which increase with age, and the fact that high circulating prorenin concentrations are present in these TGR, shed light on the kidney's role in the blood-pressure-elevating mechanisms of TGR. The viewpoint that the kidneys are not mechanistically important in this TGR model must be revised.