Genomics and Applied Biology 2018, Vol.9, No.1, 1-5
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3.3 Marinobufagenin and blood pressure
Many researches indicated that MBG was closely related to blood pressure (Anderson et al., 2008). It was thought
that EO has a more important role in blood pressure regulation, but subsequent research has found the lower
concentration of MBG can cause vasoconstriction relative to
in blood vessels of individuals. Blood
pressure
reduced in the pretreatment of hypertension model rats with the anti-MBG antibody but not in rats with
anti-EO antibody. Therefore in this genetic form of salt sensitive hypertensive rats, the increase of MBG level was
related to the formation of hypertension (Fedorova et al., 2000). Summarized from previous experimental results,
MBG regulated blood pressure from two mechanisms. On the one hand, MBG was combined with NKA on
vascular smooth muscle to reduce the transport of sodium ions, caused Intracellular Ca
2+
increases, exacerbated
the constriction of blood vessels. On the other hand, MBG combined with the NKA of the renal tubular cell
membrane to reduce the reabsorption of filtered sodium and to increase sodium retention. Recent studies found
that the relation of plasma MBG and urinary MBG excretion between systolic and diastolic blood pressure are
different, and the effect of MBG on blood pressure was related to gender.
Olga et al. found that plasma MBG was related to 24h dynamic systolic and diastolic pressure while urinary MBG
excretion just related to 24h dynamic diastolic pressure (Fedorova et al., 2015). Gender analysis of salt sensitive
hypertension patients showed that significant correlation of MBG and BP just existed in male, which might
because progestational hormone have founction of excreting sodium and competing with CTS for sodium pumps
(Morrill et al., 2008). Be same as the MBG responses of Dahl rats, subjects with MBG increased have significant
elevation in systolic and diastolic pressure after salt-load, suggesting that MBG was an important intermediary for
blood pressure elevation induced by salt in male. According to relevant clinical literature of blood pressure
monitoring in salt sensitive hypertension patients found their nocturnal blood pressure was not reduced
significantly, the nocturnal blood pressure trough is not clear or even disappear and presente
(the
morning peak of blood pressure and not enough decrease in nocturnal blood pressure), and dietary sodium
restriction or diuretic could reduce blood pressure change induced by salt. This process might be one of the
important mechanisms of target organ damage in such patients, and suggested the association between non-dipper
of hypertension patients with salt sensitivity (Yoshinaga et al., 2012; Mou et al., 2014; Xu, 2015).
3.4 Marinobufagenin and fibrosis
Marinobufagenin binding to Na
+
,K
+
-ATPase initiates profibrotic cell signaling, and heightened marinobufagenin
levels are implicated in the pathogenesis of hypertension, preeclampsia, and chronic kidney disease. Recent
studies on MBG have gradually tended to it‟s founction in fibrosis. MBG contributes to fibrosis of myocardial and
arterial and aortosclerosis. Dietary sodium restriction relieves even reverses these pathologic damage is the best
proof. Jablonski et al. (2013) found that dietary sodium restriction performed in middle-aged/older adults with
moderately elevated systolic BP would reduce urinary marinobufagenin excretion as well as systolic BP and aortic
pulsewave velocity and relieve aortosclerosis. NKA participated in signal and not activated sodium pump through
Src and Epidermal Growth Factor Receptor (EGFR) resided on fossa (Liang et al., 2007). Study found that MBG
increased the activity of NADH oxidase, oxidative stress SBP and aortic stiffness through inhibited NKA on
endothelium membrane and induce depolarization. The weak link between MBG excretion, SBP and aortic
pulsewave velocity indicated that these connections were associated with sodium intake. Although in the short
term, the effect of MBG might balance the high salt load and slow the elevation of blood pressure (Mou et al.,
2014), the vasoconstrictive effected by inhibiting NKA may be the long-term response of MBG. In addition,
Dietary sodium restriction did not reduce level of plasma MBG (Jablonski et al., 2013).
Studies have found that MBG activated pre-fibrotic signal, which could activate various signaling pathways and
EGFR signals by inhibiting NKA, leaded to degeneration of the left ventricular muscle fli-1 and inducing collagen
-1 synthesis (Elkareh et al., 2009; Liu et al., 2012; Xie et al., 2013). Study found
and
siginificant elevation of MBG level in rats with a minipump for infusing MBG and rats had uremia myocarditis
(Elkareh et al., 2007). However, the anti-MBG antibody could reverse the myocardial fibrosis of the renal failure
model and reduce the blood pressure of the pre-epileptic and salt-sensitive hypertension models (Fedorova et al.,
