ATRIAL-NATRIURETIC-FACTOR AND TRANSGENIC MICE

Atrial natriuretic factor (ANF) is a peptide hormone that induces potent but transient hypotensive and natriuretic responses on short-term administration. The role of the hormone in long-term cardiovascular regulation has remained elusive in part because of the temporal limitations of long-term infusion models and the extremely short half-life of the molecule in vivo. To circumvent these temporal limitations, a transgenic mouse model was developed that exhibits lifelong elevated plasma ANF levels. These mice are chronically hypotensive, with arterial pressures averaging 20 to 30 mm Hg less than those observed in nontransgenic siblings. In contrast, no obvious natriuretic or diuretic phenotype was observed in transgenic animals housed in metabolic cages. Thus, the mice adequately compensate for the renal effects but not the hemodynamic effects of the hormone. The ANF transgenic mice provide a tractable model system with which to study the consequences of long-term alterations of ANF expression in vivo.