Atrial natriuretic factor (ANF) is a peptide hormone that induces pote
nt but transient hypotensive and natriuretic responses on short-term a
dministration. The role of the hormone in long-term cardiovascular reg
ulation has remained elusive in part because of the temporal limitatio
ns of long-term infusion models and the extremely short half-life of t
he molecule in vivo. To circumvent these temporal limitations, a trans
genic mouse model was developed that exhibits lifelong elevated plasma
ANF levels. These mice are chronically hypotensive, with arterial pre
ssures averaging 20 to 30 mm Hg less than those observed in nontransge
nic siblings. In contrast, no obvious natriuretic or diuretic phenotyp
e was observed in transgenic animals housed in metabolic cages. Thus,
the mice adequately compensate for the renal effects but not the hemod
ynamic effects of the hormone. The ANF transgenic mice provide a tract
able model system with which to study the consequences of long-term al
terations of ANF expression in vivo.