Regional changes in cardiac and stellate ganglion norepinephrine transporter in DOCA–salt hypertension

Wehrwein, Erica A.; Novotný, Martin; Swain, Greg M.; Parker, Lindsay M.; Esfahanian, Mohammad; Spitsbergen, John M.; Habecker, Beth A.; Kreulen, David L.

doi:10.1016/j.autneu.2013.08.070

Cited by 7 publications

(4 citation statements)

References 47 publications

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“…FPKM, fragments per kilobase mapped; Gβ, G-protein beta subunit; RPS29, ribosomal protein S29. Wang et al 2002, Wehrwein et al 2013. Our study builds on the earlier finding that DOCA treatment leads to capillary rarefaction in the heart (Larouche & Schiffrin 1999).…”

Section: Figurementioning

confidence: 71%

Endothelial cell mineralocorticoid receptors oppose VEGF-induced gene expression and angiogenesis

Lother

Deng

Huck

et al. 2019

Journal of Endocrinology

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Aldosterone is a key factor in adverse cardiovascular remodeling by acting on the mineralocorticoid receptor (MR) in different cell types. Endothelial MR activation mediates hypertrophy, inflammation and fibrosis. Cardiovascular remodeling is often accompanied by impaired angiogenesis, which is a risk factor for the development of heart failure. In this study, we evaluated the impact of MR in endothelial cells on angiogenesis. Deoxycorticosterone acetate (DOCA)-induced hypertension was associated with capillary rarefaction in the heart of WT mice but not of mice with cell type-specific MR deletion in endothelial cells. Consistently, endothelial MR deletion prevented the inhibitory effect of aldosterone on the capillarization of subcutaneously implanted silicon tubes and on capillary sprouting from aortic ring segments. We examined MR-dependent gene expression in cultured endothelial cells by RNA-seq and identified a cluster of differentially regulated genes related to angiogenesis. We found opposing effects on gene expression when comparing activation of the mineralocorticoid receptor in ECs to treatment with vascular endothelial growth factor (VEGF), a potent activator of angiogenesis. In conclusion, we demonstrate here that activation of endothelial cell MR impaired angiogenic capacity and lead to capillary rarefaction in a mouse model of MR-driven hypertension. MR activation opposed VEGF-induced gene expression leading to the dysregulation of angiogenesis-related gene networks in endothelial cells. Our findings underscore the pivotal role of endothelial cell MR in the pathophysiology of hypertension and related heart disease.

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Section: Figurementioning

confidence: 71%

Endothelial cell mineralocorticoid receptors oppose VEGF-induced gene expression and angiogenesis

Lother

Deng

Huck

et al. 2019

Journal of Endocrinology

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“…Thus, the lower response to electrical stimulation in DOCA-salt rats is related mainly to presynaptic mechanisms such as a decrease in noradrenaline content (found in mesenteric and renal arteries and cardiac tissue; [4,16,23,46]) and a defect in the storage and retention of noradrenaline by granules in the sympathetic nerves [17]. The lower neurogenic vasopressor response connected with a diminished sensitivity to the noradrenaline uptake inhibitor cocaine (but without any difference in the response to noradrenaline) in pithed DOCA-salt hypertensive when compared to normotensive rats [7] also fits into this picture.…”

Section: Characterization Of Cardiovascular Parameters In Doca-salt Hmentioning

confidence: 98%

Enhanced function of inhibitory presynaptic cannabinoid CB1 receptors on sympathetic nerves of DOCA–salt hypertensive rats

et al. 2015

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“…; Wehrwein et al . ). This mechanism might be the possible pathological basis for cardiovascular disease in menopausal women.…”

Section: Discussionmentioning

confidence: 97%

Effects of oestrogen and Cimicifuga racemosa on the cardiac noradrenaline pathway of ovariectomized rats

Liu

Zhang

Liu

et al. 2017

Experimental Physiology

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What is the central question of this study? We investigated the effects of oestrogen and Cimicifuga racemosa on the stellate ganglion, cardiac noradrenaline pathway and Ca -calmodulin-dependent protein kinase II in ovariectomized rats. What is the main finding and its importance? The right stellate ganglion, but not the left, may be associated with decreased left ventricular noradrenaline content in ovariectomized rats. Oestrogen can reverse all changes caused by ovariectomy. Cimicifuga racemosa did not affect left ventricular noradrenaline, but decreased protein expression of β -adrenergic receptor and Ca -calmodulin-dependent protein kinase II. The results might explain potential effects of C. racemosa on the cardiovascular system and provide new insights into cardiovascular protection. The aim of this study was to investigate the effects of oestrogen and Cimicifuga racemosa on the stellate ganglion, cardiac noradrenaline (NA) pathway and Ca -calmodulin-dependent protein kinase II (CaMK II). Forty adult female Sprague-Dawley rats were randomly divided into the following four groups: sham operated (SHAM); ovariectomized (OVX); ovariectomized with oestrogen treatment (E2); and ovariectomized with C. racemosa treatment (iCR). After 4 weeks of treatment, the NA content was determined by high-performance liquid chromatography, and dopamine β-hydroxylase (DBH) and noradrenaline transporter (NET) expression were detected by immunohistochemistry. Western blotting was used to determine NET, β -adrenergic receptor (β -AR) and CaMK II expression. Compared with the SHAM group, body weights, DBH and NET expression in the right stellate ganglia, and NET, β -AR and CaMK II expression in the left ventricles of the OVX group were increased, whereas left ventricular NA content was decreased; DBH and NET expression in the left stellate ganglion was not significantly different. The indexes of the E2 group were similar to those of the SHAM group. Moreover, in the iCR group, DBH, NET, β -AR and CaMK II expression was decreased; NET expression and NA content of the left ventricle remained unchanged. Our conclusions are as follows. First, the right stellate ganglion, but not the left, may be associated with decreased left ventricular NA content in OVX rats. Second, oestrogen increases the left ventricular NA content and adjusts the expression of DBH and NET in the right stellate ganglion and restores β -AR and CaMK II protein expression to normal levels. Third, C. racemosa does not affect left ventricular NA, but decreases the protein expression of β -AR and CaMK II.

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Regional changes in cardiac and stellate ganglion norepinephrine transporter in DOCA–salt hypertension

Cited by 7 publications

References 47 publications

Endothelial cell mineralocorticoid receptors oppose VEGF-induced gene expression and angiogenesis

Endothelial cell mineralocorticoid receptors oppose VEGF-induced gene expression and angiogenesis

Enhanced function of inhibitory presynaptic cannabinoid CB1 receptors on sympathetic nerves of DOCA–salt hypertensive rats

Effects of oestrogen and Cimicifuga racemosa on the cardiac noradrenaline pathway of ovariectomized rats

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