Previous experiments have shown that the reduction in plasma volume ob
served after administration of atrial natriuretic factor is abolished
by splenectomy. In order to determine whether the spleen contains a fa
ctor that influences cardiorenal homeostasis, rat spleens were homogen
ized in phosphate-buffered saline, centrifuged, subjected to ultrafilt
ration (molecular weight cut-off 10,000), extracted on C-18 affinity c
olumns and dried. After reconstitution in isotonic saline, the extract
was injected I.V. into conscious rats. In response to this extract, t
here was a dose-dependent diuresis, natriuresis, kaliuresis and chloru
resis which plateaued during the second and third hours following admi
nistration. Solute-free water clearance was inversely related to urine
output. Blood pressure fell significantly from 109 +/- 3 mm Hg to 103
+/- 3 mm Hg during the first 10 min. after injection of the extract,
and tended to remain depressed thereafter. There was no accompanying i
ncrease in heart rate. We conclude that the mammalian spleen contains
a natriuretic, hypotensive factor that may play a role in cardiorenal
homeostasis.