Increased dietary NaCl potentiates the effects of elevated prorenin levels on blood pressure and organ disease.

BACKGROUND Rats with several 100-fold elevation of plasma prorenin levels due to liver-specific expression of a rat prorenin transgene have cardiac and aortic hypertrophy, renal lesions, and myocardial fibrosis. The effect of increased dietary NaCl on the phenotype of prorenin transgenic rats has not been examined. METHODS AND RESULTS We compared the effects of 0.3 and 2% dietary NaCl in wild-type and transgenic rats from 3 to 12 months of age. In comparison with wild-type rats, transgenic rats receiving 0.3% dietary NaCl had approximately 1000-fold elevation of prorenin, 1.5-fold to 2.5-fold elevation of renin concentration and activity, wild-type levels of angiotensin II, and were hypertensive with cardiac and aortic hypertrophy, and increased renal glomerular and tubulo-interstitial injury score. In wild-type rats, 2% dietary NaCl reduced angiotensin levels, produced a delayed increase in blood pressure, and caused cardiac hypertrophy and tubulo-interstitial injury. By contrast, 2% NaCl did not reduce angiotensin levels in transgenic rats, potentiated their hypertension, cardiac and aortic hypertrophy, and increased myocardial interstitial and perivascular fibrosis, without effect on glomerular or tubulo-interstitial injury score. CONCLUSION Increased dietary NaCl had a greater impact on the phenotype of transgenic than wild-type rats that may have been due, in part, to their hypertension and their failure to suppress angiotensin levels, consequent to their elevated prorenin levels.