The search for endogenous digitalis led to the isolation of ouabain from bl
ood adrenals and hypothalamus. Additional cardiotonic steroids of the carde
nolid and bufadienolide type seem to circulate in blood. Adrenal cortical c
ells in tissue culture release ouabain upon addition of angiotensin II. Oua
bain in blood is increased in 50% of Caucasians with low renin hypertension
. Analogous to other steroid hormones, cardiotonic steroid hormones in bloo
d are bound to a specific cardiac glycoside binding globulin. Since ouabain
induced growth of myocytes in tissue culture, this effect probably mediate
s by partial inhibition of the sodium pump and consecutive rise of intracel
lular Ca2+ the thickening of the wall of arteries and myocardium. PST 2238,
an antagonist of cardiac glycoside function at the sodium pump, leads in r
ats under prolonged therapy to a decrease of hypertension. The finding of o
uabain as a new adrenal hormone of the Na+ metabolism and of ouabain antago
nists opens new possibilities of therapy of hypertension and congestive hea
rt failure.