Abstract
The role of endogenous mammalian cardiotonic steroids (CTS) in the physiology and pathophysiology of the cardiovascular system and the kidneys has interested researchers for more than 20 years. Cardiotonic steroids extracted from toads or plants, such as digitalis, have been used to treat heart disease since ancient times. CTS, also called endogenous digitalis-like factors, take part in the regulation of blood pressure and sodium homeostasis through their effects on the transport enzyme called sodium–potassium adenosine triphosphatase (Na/K-ATPase) in renal and cardiovascular tissue. In recent years, there has been increasing evidence showing deleterious effects of CTS on the structure and function of the heart, vasculature and kidneys. Understanding the role of CTS may be useful in the development of potential new therapeutic strategies.
Highlights
Cardiotonic steroids are a group of steroid hormones that circulate in the blood and are excreted in the urine
Ouabain was found in the serum of healthy volunteers and in patients with congestive heart failure, hypertension and kidney failure [3]
In α1+/− mice myocytes, MBG failed to induce this signaling pathway. It caused the activation of caspase 9 and, induced myocyte apoptosis [57]. These results indicate that a reduction in Na/K-ATPase enables MBG to induce cardiac myocyte apoptosis, leading to heart failure
Summary
Apart from the physiological role of CTS in the regulation of sodium content, blood volume and pressure, CTS take part in the pathological adaptation resulting in hypertension. A high sodium diet results in a faster pulse wave velocity (PWV), indicating arterial stiffening, which precedes the development of hypertension with aging [36,37,38] Observations from studies, both in animals and humans, have shown that an increased salt intake associates with elevated MBG levels. The administration of an anti-MBG antibody to Dahl salt-sensitive rats and in NaCl-supplemented pregnant rats with elevated MBG levels was associated with the restoration of vascular sodium pump activity and reduction in blood pressure This observation indicates that MBG exerts its pressor effects by inhibiting Na/K-ATPase in vascular smooth muscle [47]. Considering the above, MBG may become an early biomarker of increased cardiovascular risk
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