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2018 ; 18
(1
): 705-714
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Candesartan targeting of angiotensin II type 1 receptor demonstrates benefits for
hypertension in pregnancy via the NF??B signaling pathway
#MMPMID29845261
Zhao X
; Wang X
Mol Med Rep
2018[Jul]; 18
(1
): 705-714
PMID29845261
show ga
Hypertensive disorders may be a complication of pregnancy and are characterized
by the high blood pressure. Evidence suggests that alterations in the
renin?angiotensin?aldosterone system and the sympathetic nervous system are
associated with gestational hypertension. Angiotensin II type 1 receptor
(Ang?IITR) is a potential target in the progression of gestational hypertension.
Candesartan is selective Ang?IITR antagonist that may act against
vasoconstriction and reduces peripheral vascular resistance. The aim of the
present study was to evaluate the efficacy of Candesartan and the underlying
molecular mechanism of the nuclear factor??B (NF??B) signaling pathway in the
progression of gestational hypertension in a mouse model. Expression and activity
of Ang?IITR was evaluated in a mouse model of gestational hypertension prior to
and post?treatment of Candesartan both in vitro and in vivo. It was determined
whether Candesartan treatment reduces higher blood pressure activated the renal
renin?angiotensin system and a prognostic marker, soluble endoglin, and its
associated gene in mice with gestational hypertension. Angiotensin?converting
enzyme plasma levels and activity were also evaluated in the present study.
Cytoplasmic and nuclear immunostaining of NF??B and associated proteins
transforming growth factor ? (TGF??) and endoglin was enhanced in vascular
endothelial cells and mice with gestational hypertension. Soluble fms?like
tyrosine kinase 1 (sFlt?1), insulin resistance homeostasis model assessment score
and associated cardiovascular risk factors also were measured. Results
demonstrated that angiotensin and Ang?IITR expression levels were upregulated in
mice with gestational hypertension and were downregulated by Candesartan
treatment. Renal renin?angiotensin and soluble endoglin were also improved in
mice in the Candesartan?treated group. In addition, Candesartan treatment
enhanced NF??B activity, as well as TGF?? and vascular endothelial growth factor
expression which led to improved levels of sFlt?1, insulin resistance homeostasis
and associated cardiovascular risk factors. Gestational hypertension was markedly
improved by treatment of Candesartan compared with the control. In conclusion,
the findings of the present study suggested that the NF??B signaling pathway may
be involved in with Candesartan?mediated Ang?IITR for the treatment of
gestational hypertension.