Natriuretic peptide expression in the heart of the TTR-ANP transgenic mouse-Comparison to the normal heart.

The transgenic mice, TTR-ANP, carrying a fusion gene comprising the transthyretin promoter and the atrial natriuretic peptide (ANP) structural sequence, are known to have elevated ANP plasma levels as well as lowered blood pressure levels. On the other hand, it is not known whether these transgenic mice show changed natriuretic peptide (NP) expression patterns in the heart. Therefore, we examined the distribution of NPs in the myocardium and the conduction system of transgenic mice overexpressing ANP, as well as in wild-type littermates. The hearts were serially sectioned and processed for immunohistochemistry, with antisera against ANP and brain natriuretic peptide (BNP). Florescence microscopy was performed for qualitative analysis. Immunoreactivity for ANP and BNP was detected to a similar degree in the conduction system of both transgenic and wild-type mice. The nodal tissues never exhibited immunoreactions for ANP or BNP, whereas Purkinje fibers of the atrioventricular junctional tissue, bundle branches, and the peripheral Purkinje fiber network exhibited specific immunoreactivity. Atrial and ventricular myocytes of both transgenic and wild-type mice exhibited ANP and BNP to a similar extent. This is the first study examining the expression pattern of NPs in the cardiac conduction system of the mouse as well as the pattern of ANP and BNP expression in the conduction system of TTR-ANP transgenic mice and its wild-type siblings. The findings in this study suggest that ectopic ANP expression and release do not repress cardiac production of ANP.