Ouabain has recently been identified in mammalian plasma with an appar
ent adrenocortical origin. The objectives of the present study were to
determine whether boiled plasma supernatants (BPS) from spontaneously
hypertensive rats (SHR) contained elevated levels of material able to
inhibit Rb-86 uptake, an indicator of sodium pump activity, compared
with Wistar-Kyoto rats (WKY). Furthermore, the effect of increasing di
etary calcium content from 1 to 3% on Rb-86-uptake inhibitory activity
in plasma was examined. BPS from SHR and WKY consuming 1% calcium con
tained sodium pump inhibitory activity equivalent to 16.43 +/- 0.23 an
d 5.08 +/- 0.10 ng ouabain/ml, respectively (P < 0.0001). Increasing d
ietary calcium intake to 3% reduced plasma ouabainlike activity (OLA)
to 9.97 +/- 0.20 ng/ml (P < 0.0001) in SHR but was without effect in W
KY (5.39 +/- 0.05; not significant). It was then determined whether th
e plasma Rb-86-uptake inhibition could be attributed to authentic ouab
ain. In WKY plasma pools the percentage of OLA attributable to authent
ic ouabain was 38.0% by radioimmunoassay and 56.7% by Rb-86-uptake ass
ay. In SHR these values were 3.8% and <7.1%, respectively. Whereas the
data in the present study provide confirmation of the presence of oua
bain in rat plasma, ouabain does not account for the elevated OLA in S
HR plasma reported here and elsewhere. This hypertensinogenic cardioto
nic steroid appears to be appropriately downregulated in SHR rats.