Angiotensin II-superoxide-NFκB signaling and aortic baroreceptor dysfunction in chronic heart failure

Abstract

Chronic heart failure (CHF) affects approximately 5.7 million people in the United States. Increasing evidence from both clinical and experimental studies indicates that the sensitivity of arterial baroreflex is blunted in the CHF state, which is a predictive risk factor for sudden cardiac death. Normally, the arterial baroreflex regulates blood pressure and heart rate through sensing mechanical alteration of arterial vascular walls by baroreceptor terminals in the aortic arch and carotid sinus. There are aortic baroreceptor neurons in the nodose ganglion (NG), which serve as the main afferent component of the arterial baroreflex. Functional changes of baroreceptor neurons are involved in the arterial baroreflex dysfunction in CHF. In the CHF state, circulating angiotensin II (Ang II) and local Ang II concentration in the NG are elevated, and AT1R mRNA and protein are overexpressed in the NG. Additionally, Ang II-superoxide-NFκB signaling pathway regulates the neuronal excitability of aortic baroreceptors through influencing the expression and activation of Nav channels in aortic baroreceptors, and subsequently causes the impairment of the arterial baroreflex in CHF. These new findings provide a basis for potential pharmacological interventions for the improvement of the arterial baroreflex sensitivity in the CHF state. This review summarizes the mechanisms responsible for the arterial baroreflex dysfunction in CHF.

Hydrogen Sulfide Facilitates the Impaired Sensitivity of Carotid Sinus Baroreflex in Rats with Vascular Calcification

“…Via the baroreflex, an increase in blood pressure causes reduced heart rate and stroke volume and enhanced vasodilatation, which restores blood pressure to normal levels (Benarroch, 2008 ). Baroreflex sensitivity is considered a comprehensive marker of the universal integrity of the autonomic nervous system (Robinson and Carr, 2002 ), which can be regulated by many endogenous active substances, such as angiotensin II and H 2 S (Zhang et al, 2015 ).…”

Effect of captopril on radiation-induced TGF-β1 secretion in EA.Hy926 human umbilical vein endothelial cells

“…In the resting state, NFκB remains inactive in the cytosol by tightly binding to the specific inhibitor of κBα (IκBα) [ 18 ]. In response to multiple stimuli in pathophysiological conditions, IκB molecules are phosphorylated, ubiquitinated and then degraded, thus releasing their inhibition on NFκB [ 9 ]. To examine whether NFκB activation status in EA.Hy926 cells is affected by radiation, nuclear proteins were extracted at different time points after the last irradiation and Iκ-Bα protein levels and NF-κB activity were examined by western blotting and EMSA assay, respectively.…”

“…In the kidney, Ang II was shown to induce fibrogenesis through NF-κB-dependent upregulation of ICAM-1 [ 8 ]. Moreover, the Ang II/superoxide/NFκB signaling pathway was shown to regulate the excitability of aortic baroreceptors during chronic heart failure [ 9 ]. Ang II receptor antagonists inhibit various signaling pathways involved in the regulation of inflammation, apoptosis and angiogenesis, both in cancer cells and in normal cells, and have shown effectiveness in the treatment of cancer by inhibiting tumor progression, vascularization and metastasis [ 10 ].…”

Neuro-Humoral Disbalance in Chronic Heart Failure: Classic and Modern Perspectives

“…Эти результаты показывают новую и потенциально уни-кальную роль miR-133a в регуляции A-II [5]. Повыше-ние уровня A-II (циркулирующего, а также локальная концентрация A-II в узловом ганглии) наблюдается очень часто у пациентов с CH или хронической бо лезнью почек [6], при этом, A-II через рецептор 1 типа вызывает разрушение и апоптоз мышечного белка и ингибирует пролиферацию и регенерацию клеток-сателлитов, что, вероятно, способствует кахек-сии при ХСН и хронических заболеваниях почек. Напротив, экспрессия рецептора типа 2 (AT2R) инду-цируется во время дифференцировки клеток-сателли-тов и это потенцирует регенерацию мышц [7].…”