MOUSE AND RAT PLASMA-RENIN CONCENTRATION AND GENE-EXPRESSION IN (MREN2)27 TRANSGENIC RATS

The (mRen2)27 transgenic rat [TGR(mRen2)27] is said to have low plasma levels of active renin. We used a direct radioimmunoassay (RIA) for m ouse submaxillary renin, as well as an indirect enzyme-kinetic assay b ased on the generation of angiotensin I with modification of the pH op timum, to measure rat and mouse plasma renin activity (PRA), plasma re nin concentration (PRC), and plasma prorenin in TGR before and after l isinopril. The relationship between rat PRC and %rat kidney extract wa s steepest at pH 6.0 and flat at pH 8.5, whereas the relationship betw een mouse PRC and purified mouse renin was steepest at pH 8.5 and flat at pH 6.0. Mouse PRC was highly correlated with direct RIA measuremen ts (r = 0.93). PRA before lisinopril was little influenced by pH, wher eas the increase with lisinopril was greatest at pH 6.5. PRC before li sinopril was fourfold higher at pH 8.5 compared with that at pH 6.0. L isinopril increased both PRC values but reversed the pH dependency. Pr orenin was fourfold higher at pH 8.5 compared with that at pH 6.0 and decreased slightly with lisinopril. Renal renin concentration was high er at pH 6.0 than at pH 8.5. With Lisinopril, renal renin concentratio n increased at both pH values. Mouse PRC was not changed by lisinopril . Ribonuclease protection assay showed both rat and mouse renin gene e xpression in the kidney, which increased with lisinopril. Thus TGR hav e circulating active rat and mouse renin and prorenin. The notion that TGR are a ''low renin'' model should be revised.