Tissue activity of circulating prorenin

Both renin and its biosynthetic precursor, prorenin, are secreted into the circulation of mammals. Although the circulating levels of prorenin can exceed those of renin by as much as 100-fold in certain conditions, there is no evidence that prorenin contributes to the synthesis of circulating angiotensin peptide synthesis or increased blood pressure (BP). In the current study, we have generated a transgenic mouse line that overexpresses human prorenin in the liver and have mated these mice to a second mouse line expressing human angiotensinogen in the heart. Double-transgenic progeny display a selective increase in angiotensin I content in the heart (but not the plasma) as compared to the single-transgenic mice. These results are consistent with a model in which circulating prorenin is taken up by tissues where it can contribute to the local synthesis of angiotensin peptides. This finding may explain some of the pathologies associated with high circulating prorenin levels.