Salusin-β in rostral ventrolateral medulla increases sympathetic outflow and blood pressure via superoxide anions in hypertensive rats

Zhang, Lingli; Ding, Lei; Zhang, Feng; Gao, Run; Chen, Qi; Li, Yuehua; Kang, Yu‐Ming; Zhu, Guo‐Qing

doi:10.1097/hjh.0000000000000143

Cited by 28 publications

(33 citation statements)

References 42 publications

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“…8 Previous studies in our lab have shown that central salusin- β contributes to sympathetic activation, arginine vasopressin release and hypertension. 9, 10, 11 Salusin- β promotes proliferation of vascular smooth muscle cells (VSMCs) and vascular fibrosis. 12 ROS production in VSMCs mediates salusin- β -induced foam cell formation and monocyte adhesion, 13 VSMCs migration and intimal hyperplasia after vascular injury.…”

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confidence: 99%

Salusin-β contributes to oxidative stress and inflammation in diabetic cardiomyopathy

Zhao

Zhou

et al. 2017

Cell Death Dis

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Salusin-β accelerates inflammatory responses in vascular endothelial cells, and increases oxidative stress in vascular smooth muscle cells. Plasma salusin-β levels were increased in diabetic patients. This study was designed to determine whether salusin-β is involved in the pathogenesis of diabetic cardiomyopathy (DCM), and whether knockdown of salusin-β attenuates cardiac inflammation and oxidative stress in rats with DCM. H9c2 or neonatal rat cardiomyocytes were incubated with 33.3 mM of glucose to mimic the high glucose (HG) in diabetes. Streptozotocin and high-fat diet were used to induce type 2 diabetes in rats. HG induced salusin-β expression in H9c2 cells. Salusin-β caused greater responses of oxidative stress, NFκB activation and inflammation in HG-treated H9c2 cells than these in control H9c2 cells. Diphenyleneiodonium (a NAD(P)H oxidase inhibitor) or N-acetylcysteine (an antioxidant) inhibited the salusin-β-induced NFκB activation and inflammation. Bay11-7082 (a NFκB inhibitor) attenuated salusin-β-induced inflammation but not oxidative stress. Knockdown of salusin-β prevented the HG-induced oxidative stress, NFκB activation and inflammation in neonatal rat cardiomyocytes. Silencing salusin-β with adenoviruse-mediated shRNA had no significant effects on blood glucose and insulin resistance, but attenuated ventricular dysfunction in diabetic rats. Oxidative stress, NFκB activation, inflammation, salusin-β upregulation in myocardium of diabetic rats were prevented by knockdown of salusin-β. These results indicate that salusin-β contributes to inflammation in DCM via NOX2/ROS/NFκB signaling, and that knockdown of salusin-β attenuates cardiac dysfunction, oxidative stress and inflammation in DCM.

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confidence: 99%

Salusin-β contributes to oxidative stress and inflammation in diabetic cardiomyopathy

Zhao

Zhou

et al. 2017

Cell Death Dis

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“…Surgery for blood pressure recording was carried out under anesthesia with intraperitoneal injection of urethane (800 mg/kg) and achloralose (40 mg/kg). The depth of anesthesia was determined by the absence of corneal reflexes and paw withdrawal response to a noxious pinch [11]. At the end of the experiment, the rats were euthanized with an overdose of pentobarbital sodium (150 mg/kg, iv).…”

Section: Animalsmentioning

confidence: 99%

“…The rats were warmed for 10-20 min at 28°C before the measurements in order to allow detection of tail artery pulsations and to achieve the steady pulse level. SBP was obtained by averaging 10 measurements [11,20]. Mean arterial pressure (MAP) and heart rate (HR) were recorded under anesthesia with intraperitoneal injection of urethane (800 mg/kg) and a-chloralose (40 mg/kg).…”

Section: Measurement Of Blood Pressurementioning

confidence: 99%

“…The initial 18 amino acids of human salusin-β have high homology with the estimated N-terminal sequence of rat salusin, but human salusin-α have a very big difference in the sequence compared with rat salusin [8]. Central salusin-β contributed to sympathetic activation, arginine vasopressin release and hypertension, and plasma salusin-β level was increased in renovascular hypertensive rats [9][10][11][12]. Plasma salusin-β levels in subjects with diabetes mellitus, coronary artery disease, and cerebrovascular disease showed distinctly higher levels than healthy controls, and it may be taken as an indicator of systemic vascular diseases [13].…”

Section: Introductionmentioning

confidence: 96%

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Salusin-β contributes to vascular remodeling associated with hypertension via promoting vascular smooth muscle cell proliferation and vascular fibrosis

Sun

Liu

Zhang

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Vascular smooth muscle cell (VSMC) proliferation and vascular fibrosis are closely linked with hypertension and atherosclerosis. Salusin-β is a bioactive peptide involved in the pathogenesis of atherosclerosis. However, it is still largely undefined whether salusin-β is a potential candidate in the VSMC proliferation and vascular fibrosis. Experiments were carried out in human vascular smooth muscle cells (VSMCs) and in rats with intravenous injection of lentivirus expressing salusin-β. In vitro, salusin-β promoted VSMCs proliferation, which was attenuated by adenylate cyclase inhibitor SQ22536, PKA inhibitor Rp-cAMP, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478, ERK inhibitor U0126 or cAMP response element binding protein (CREB) inhibitor KG501. It promoted the phosphorylation of ERK1/2, CREB and EGFR, which were abolished by SQ22536 or Rp-cAMP. Furthermore, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 diminished the salusin-β-evoked ERK1/2 and CREB phosphorylation. On the other hand, salusin-β increased collagen-I, collagen-III, fibronectin and connective tissue growth factor (CTGF) mRNA and phosphorylation of Smad2/3, which were prevented by ALK5 inhibitor A83-01. In vivo, salusin-β overexpression increased the media thickness, media/lumen ratio coupled with ERK1/2, CREB, EGFR and Smad2/3 phosphorylation, as well as the mRNA of collagen-I, collagen-III, fibronectin, transforming growth factor-β1 (TGF-β1) and CTGF in arteries. Moreover, salusin-β overexpression in rats caused severe hypertension. Intravenous injection of salusin-β dose-relatedly increased blood pressure, but excessive salusin-β decreased blood pressure and heart rate. These results indicate that salusin-β promotes VSMC proliferation via cAMP-PKA-EGFR-CREB/ERK pathway and vascular fibrosis via TGF-β1-Smad pathway. Increased salusin-β contributes to vascular remodeling and hypertension.

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“…It has been demonstrated that the sympathetic activity of obese rats (4,24), renovascular hypertensive rats (5,25,26) and SHRs (6,27,28) is enhanced compared with normotensive rats. Hexamethonium is a ganglionic blocker (10,11) and reduces blood pressure in SHR and Wistar rats (8).…”

Section: A B Cmentioning

confidence: 99%

Hexamethonium attenuates sympathetic activity and blood pressure in spontaneously hypertensive rats

Gong

Sun

Zhou

et al. 2015

Molecular Medicine Reports

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Abstract. Sympathetic activity is enhanced in heart failure and hypertensive rats. The aims of the current study were: i) To investigate the association between renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to intravenous injection of the ganglionic blocker hexamethonium; and ii) to determine whether normal Wistar rats and spontaneously hypertensive rats (SHRs) differ in their response to hexamethonium. RSNA and MAP were recorded in anaesthetized rats. Intravenous injection of four doses of hexamethonium significantly reduced the RSNA, MAP and heart rate (HR) in the Wistar rats and SHRs. There were no significant differences in the RSNA, MAP or HR between Wistar rats and SHRs at the two lowest doses of hexamethonium. However, the two highest doses of hexamethonium resulted in a greater reduction in the RSNA and MAP in SHRs compared with Wistar rats. There was a significant positive correlation between the alterations in RSNA and MAP in response to the intravenous injection of hexamethonium in the Wistar rats and SHRs. There were no significant differences in the timing of the maximal effects on RSNA, MAP or HR or in recovery following hexamethonium treatment. These results suggest that there is an association between the RSNA and MAP response to intravenous injection of hexamethonium and that the alterations in MAP in response to hexamethonium may be used to evaluate basal sympathetic nerve activity.

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Salusin-β in rostral ventrolateral medulla increases sympathetic outflow and blood pressure via superoxide anions in hypertensive rats

Abstract: Salusin-β in the RVLM increases sympathetic outflow, blood pressure and heart rate via NAD(P)H oxidase-derived superoxide anions in renovascular hypertensive rats.

Cited by 28 publications

References 42 publications

Salusin-β contributes to oxidative stress and inflammation in diabetic cardiomyopathy

Salusin-β contributes to oxidative stress and inflammation in diabetic cardiomyopathy

Salusin-β contributes to vascular remodeling associated with hypertension via promoting vascular smooth muscle cell proliferation and vascular fibrosis

Hexamethonium attenuates sympathetic activity and blood pressure in spontaneously hypertensive rats

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