Figure 4.

Proposed biosynthesis and function of endogenous cardiotonic steroids

Synthesis of endogenous cardiotonic steroids occurs in the adrenal cortex from cholesterol and is proposed to be under the control of adrenocorticotropic hormone (ACTH) and angiotensin II. These are produced in response to high salt and the resultant ouabain synthesis in the hypothalamus. Acute effects of endogenous cardiotonic steroids are mediated via inhibition of the NKA and lead to increased cardiac output, Na⁺ excretion and vasoconstriction (NKA isoform-specific effects in each tissue are shown in red). Chronic exposure to cardiotonic steroids leads to adaptational remodelling changes of the affected tissue, possibly resulting in hypertrophy, fibrosis, hypertension and arrhythmogenesis. MBG, marinobufagenin. Adapted from Pavlovic (2014).