With an exception of few reports

the plasma concentration of ouabain and marinobufagenin

mostly studied cardiotonic steroids (CTS) assessed by immunoassay techniques

is less than 1 nM. During the last 3 decades

the implication of these endogenous CTS in the pathogenesis of hypertension and other volume-expanded disorders is widely disputed. The threshold for inhibition by CTS of human and rodent α1-Na

K-ATPase is ∼1 and 1000 nM

respectively

that rules out the functioning of endogenous CTS (ECTS) as natriuretic hormones and regulators of cell adhesion

cell-to-cell communication

gene transcription and translation

which are mediated by dissipation of the transmembrane gradients of monovalent cations. In several types of cells ouabain and marinobufagenin at concentrations corresponding to its plasma level activate Na

K-ATPase

decrease the [Na

+

]

i

/[K

+

]

i

-ratio and increase cell proliferation. Possible physiological significance and mechanism of non-canonical Na

+

i

/K

+

i

-dependent and Na

+

i

/K

+

i

-independent cell responses to CTS are discussed.