THE RENIN-ANGIOTENSIN SYSTEM AND RENAL-FUNCTION IN TRANSGENIC (MREN2)27 RATS

The transgenic rat (TGR) (mRen2)27 was the first hypertensive transgen ic rat model developed. The model is unique in that it allows studying the effects of a single gene, namely the mouse salivary gland renin g ene (mRen2), in the rat. The transgene is expressed in various rat tis sues, including the central nervous system, adrenal gland, and the kid ney. TGR exhibit a rightward shifted pressure-natriuresis curve that i s overwhelmingly angiotensin II (Ang II) dependent. The mRen2 transgen e, the rat's own renin gene, angiotensinogen, and the type 1 Ang II re ceptor, AT(1), are all expressed in the kidneys of TGR. The rat's own renin gene is regulated normally in renal tissue, while the mRen2 tran sgene operates independently of blood pressure. These results, coupled with findings that the mRen2 transgene product converts rat angiotens inogen more effectively than endogenous rat renin, that the TGR may ha ve high circulating mouse renin levels which increase with age, and th e fact that high circulating prorenin concentrations are present in th ese TGR, shed light on the kidney's role in the blood-pressure-elevati ng mechanisms of TGR. The viewpoint that the kidneys are not mechanist ically important in this TGR model must be revised.