Genomics and Applied Biology 2018, Vol.9, No.1, 1-5
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Dahl rat discovered MBG had inseparable relation with EO compared level of EO and MBG in central and
peripheral found them have same model. Transient responses of endogenous ouabain preceded the persistent
elevation of MBG excretion in acute and
chronic
NaCl-loaded DS rats (Fedorova et al., 2000; 2005; 2007).
In the acute NaCl-loaded experiment, transientpeak responses of endogenous ouabain in the amygdale,
hippocampus preceded stimulation of endogenous ouabain in the hypothalamus and pituitary
，
whereafter
，
level of
MBG excretion elevated persistently. This model suggested persistent elevation of MBG excretion may stumilated
by EO sharp increase in brain. Consistented with the hypothesis, the pretreatment of NaCl-loaded rats with the
anti-MBG antibody prevented BP elevation, reduced renal sodium excretion and restored the activity of the
sodium pump in the proximal convoluted tubules (Fedorova et al., 2007). Subsequently, Olga V et al.
implemented acute salt-load to Dahl rats, the level of EO transient rised in hypophysis cerebri, plasma and kidney
while the level of renal MBG excretion and plasma MBG elevated persistently, the level of AngⅡ in hypophysis
cerebri and adrenal cortex also increased. These consequences caused renal sodium pump activity reducing,
sodium excretion increasing and blood pressure elevation, which could be alleviated by anti-MBG antibody.
Anti-EO antibody could reduce elevation of AngⅡ
in hypophysis, losartan had similar fountion with anti-EO
antibody, but didn‟t impact EO release. So different from the previous consequences that AngⅡ secreted a variety
of steroid, including EO, via AT2 receptors pathway, the experiments revealed adrenal cortical cells secreted MBG
via AT1 receptor pathway as this approach can be inhibited by Losartan (Fedorova et al., 2005). Fedorova et al.
had new progress in synthesized of MBG.
They found MBG producted in placenta and adrenal cortex via a
„acidic‟ bile acid pathway outside the liver like amphibian. Steroids are derived from cholesterol through the
traditional steroidogenesis pathway initiated by enzyme CYP11A1, and via the acidic bile acid pathway make it
become bufadienolide, which is controlled by enzyme CYP27A1 (Fedorova et al., 2015). The mechanism of
marinobufagenin biosynthesis in mammals, however, remains unknown. But These findings will help to
understand the role of marinobufagenin in highly prevalent human cardiovascular diseases.
3.2 Marinobufagenin and sodium excretion
The bioactive steroid, marinobufagenin, is a specific ligand of Na
+
,K
+
-ATPase (NKA), which can inhibit the
founction of NKA. MBG is initially defined as the “natriuretic hormone” suggests that its sodium excretion was
the most important founction be attented. Previous studies have shown that MBG was positively correlated with
urinary sodium excretion. In the early stages of the long-term salt load, MBG reactively increased blood pressure
to raise sodium excretion as response to sodium elevation in body. In the case of long-term sodium salt load, the
natriuretic effect of MBG was difficult to compensate, but the amount of excretion continues to rise, and the
excretion of MBG is gradually increasing. The level of renal MBG and urinary MBG decreased, but the plasma
MBG did not.
Dietary sodium restriction reduced urinary marinobufagenin excretion and that might relieve systolic BP and
aortic stiffness (aortic pulse-wave velocity) by reducing oxidative stress (Jablonski et al., 2013). Endogenous
marinobufagenin increased for self-adaption in salt sensitive hypertension, which reduced proximal tubular
sodium reabsorption and promoted sodium excretion through inhibiting Na
+
,K
+
-ATPase α
1
. This mechanism
resulted in sustained stimulates biosynthesis and overproduction
of MBG while sodium excretion is sufficient.
Overproduction
of MBG inhibited Na
+
,K
+
-ATPase
α
1
and enhanced vasoconstriction which
leaded to
prehypertension. 24 hours urinary sodium excretion were not significantly different in salt-sensitive subjects and
non-salt-sensitive subjects, but the nocturnal urine sodium excretion of non-salt-sensitive people was significantly
lower than that of salt sensitive and the percentage of nocturnal urinary sodium in total is also significantly higher
than that of non-salt sensitive people (Mou et al., 2014). The main reason is that the salt sensitive person's kidneys
have a natriuretic deficiency, which causes the sodium peak to be delayed after high salt intake, and the sodium
excretion capacity decreases, resulting in remaining sodium retention. Body reconstructs stress urinary natriuretic
function to extrect the sodium retention in the body and increase nocturnal sodium excretion passively, then
compensatory elevated blood pressure at night and showed Non-dipper change.
