1.Actions of aldosterone in the cardiovascular system: the good, the bad, and the ugly?
Michael Gekle & Claudia Grossmann. Pflugers Arch - Eur J Physiol (2009) 458:231–246
Thus, the physiological role of endogenous ouabains may be limited. This does not exclude their contribution to pathophysiological states. Enhanced levels of endogenous ouabains in hypertensive patients have been reported, and a central role for marinobufagenin in the pathogenesis of experimental uremic cardiomyopathy, a condition with elevated serum aldosterone, has been proposed. Of note, the ability of marinobufagenin to interfere with MR-dependent gene regulation has been described, although the systemic significance of such an interaction has to be tested further. Furthermore, plasma marinobufagenin-like and ouabain-like immunoreactivity increases during experimental saline volume expansion. Thus, an attractive, yet unproven, hypothesis to explain aldosterone-induced hypertension is a synergistic action of aldosterone and endogenous ouabain in VSMC. This hypothesis would also explain the observation that aldosterone is especially effective in increasing blood pressure under conditions of high sodium diet-a condition which supports the secretion of endogenous ouabain.
2.Regulatory Function of the Na,KATPase α2Isoform
I. I. Krivoi. Biophysics, 2012, Vol. 57, No. 5, pp. 592–606.
The fact that the αsubunit of Na,KATPase serves as a specific receptor for cardiac glycosides, it has led to appearance of hypothesis about existence of endog enous ligands to this receptor, representing physiological modulators of Na,KATPase activity. From various tissues and biological fluids of animals and man, isolated were ouabain, digoxin, marinobufagenin, telocinobufagenin and other inhibitors of Na,K-ATPase. These ligands also have steroid structure and supposedly are synthesized in the adrenal cortex, hypothalamus and hypophysis. At the present time the most studied are endogenous analogs of ouabain and marinobufagenin. The level of these endogenous circulating CTS in physiological conditions lies in a subnanomolar range. However in hypoxia, intense physical load, in pregnant women and newborns, and also in a series of diseases (chronic renal failure, hypertension, acute cardiac failure, affective nervous disorders etc.) noted is a substantial elevation of the level of endogenous CTS.
3.Modulating Effect of the Cardiotonic Steroid Marinobufagenin on Slow Sodium Channels
T. N. Shelykh, V. B. Plakhova, S. A. Podzorova. Doklady Biological Sciences, 2014, Vol. 458, pp. 278–280
Pharmacological agents capable of reducing the nociceptors excitability due to a decrease in the voltage sensitivity of the activation gate structure of Naν1.8 slow sodium channels could play the role of analgesics. Our data suggest that marinobufagenin could play the role of the modulator of slow sodium channel activity. The discovered effect of the reduction of Naν1.8 channel voltage sensitivity by marinobufagenin may be caused by one of the two mechanisms.
The first of them, transducermediated one, is possibly triggered by the effect of the experimental agent on its wellknown molecular target, Na+,K+ ATPase linked to slow sodium channels. The second mechanism may be activated by the direct interaction of marinobufagenin with Naν1.8 channels. Further experiments will allow choosing one of these alternative hypotheses. However, it is evident that any of the two possible mechanisms of action of the given bufadienolide would lead to a decrease in nociceptor excit ability. The physiological significance of this effect cannot be overestimated, because it is known that the endogenous cardiotonic steroid ouabain is a strong analgesic.
4.The Effect of Marinobufagenin on the Growth and Proliferation of Cells in the Organotypic Culture
V. A. Penniyaynen, A. V. Kipenko, E. V. Lopatina, A. Ya. Bagrov, and B. V. Krylov. Doklady Biological Sciences, 2015, Vol. 462, pp. 164–166
Marinobufagenin, the inhibitor of the Na+,K+ ATPase, belongs to the group of cardiotonic bufadienolide steroids. It was first discovered in the skin of the toad Bufo marinus, where its physiological function consists in the regulation of sodium excretion. In the 1990s, bufadienolide compounds were discovered in mammals. The concentrations of the endogenous digitalislike factors in the systemic circulation are usually very low, the concentration of ouabain varying in the range of 300–1000 pM and that of marinobufagenin being about 400 pM. Increased levels of endogenous marinobufagenin can be detected in a number of pathological states, such as essential hypertension, cardiac infarction, diabetes mellitus, and chronic renal dysfunction. It was determined that marinobufagenin contributes to the development of generalized vasoconstriction and gestational toxicosis.