Candesartan targeting of angiotensin II type 1 receptor demonstrates benefits for hypertension in pregnancy via the NF‑κB signaling pathway.

Abstract

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-κB (NF-κB) 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-κB and associated proteins transforming growth factor β (TGF-β) 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-κB activity, as well as TGF-β 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-κB signaling pathway may be involved in with Candesartan-mediated Ang-IITR for the treatment of gestational hypertension.