The effect of nebivolol on asymmetric dimethylarginine system in spontaneously hypertension rats

Wang, Yan; Zhang, Mingsheng; Liu, Yunfeng; Liu, Yu; Chen, Min

doi:10.1016/j.vph.2010.12.001

Cited by 32 publications

(26 citation statements)

References 30 publications

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“…Recently, ROS has been thought as an intracellular signal molecule, which plays an important role in causing apoptotic cell death. A previous study reported that ADMA concentration-dependently increased intracellular ROS production via Buncoupling of NOS activity^in endothelial cells (Wang et al 2011). Our present results also confirmed that ADMA significantly increased intracellular ROS production as measured by the oxidative stress-sensitive dye DCFH-DA, and downregulated eNOS expression in HBMECs.…”

Section: Discussionsupporting

confidence: 91%

Probucol Protects Against Asymmetric Dimethylarginine-Induced Apoptosis in the Cultured Human Brain Microvascular Endothelial Cells

Zhao

Gao

et al. 2015

J Mol Neurosci

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Asymmetric dimethylarginine (ADMA) is emerging as a key contributor to endothelial dysfunction. The drug probucol was reported to have an anti-lipid peroxidation effect and improve endothelial dilation function. But little is known about the protective effect of probucol on ADMA-induced human brain microvascular endothelial cell (HBMEC) injury and its underlying mechanisms. Therefore, in this study, we investigated the effect of probucol on ADMA-induced HBMEC injury and its potential mechanisms. Results showed that probucol protected against ADMA-induced HBMEC injury in a dose-dependent manner; probucol pretreatment also significantly reduced the level of reactive oxygen species (ROS) and malondialdehyde (MDA), downregulated the expression of pro-apoptotic gene Bax and caspase-3 activity, as well as increased the brain-derived neurotrophic factor (BDNF) release and promoted anti-apoptotic gene Bcl-2 and eNOS expression in the cultured HBMECs. Furthermore, we found that ADMA significantly increased the phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38, while probucol pretreatment effectively inhibited ADMA-induced JNK and p38 phosphorylation in HBMECs. In conclusion, our present results demonstrated that probucol protected against ADMA-induced HBMEC injury and suppressed oxidative stress through the JNK/p38 MAPK pathway, which was the potential underlying mechanism of HBMEC injury in ischemic cerebrovascular disease.

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Section: Discussionsupporting

confidence: 91%

Probucol Protects Against Asymmetric Dimethylarginine-Induced Apoptosis in the Cultured Human Brain Microvascular Endothelial Cells

Zhao

Gao

et al. 2015

J Mol Neurosci

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“…22 Our previous study showed that nebivolol treatment significantly increased plasma NO and NO synthase (NOS) activity, and up-regulated endothelial NOS (eNOS) mRNA expression. 23 The specific mechanism of nebivolol is particularly relevant in hypertension, where NO dysfunction occurs. Nebivolol may induce NO production via activation of β 3 -adrenergic receptors 24 or an estrogen receptor, 25 which has led to clinically significant improvements in hypertensive patients observed after treatment with this drug.…”

Section: Discussionmentioning

confidence: 99%

Nebivolol treatment improves resistant arterial function and reduces ventricular hypertrophy and angiotensin II in spontaneously hypertension rats

Wang

Zhang

Liu

2012

J Renin Angiotensin Aldosterone Syst

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Objective: The objective of this article is to assess the effects of nebivolol on resistant vascular reactivity, ventricular hypertrophy and the renin-angiotensin system in spontaneously hypertension rats (SHR). Methods: Rats were divided into: SHR treated with nebivolol (8 mg/kg, i.g.)/atenolol(80 mg/kg, i.g.); SHR control group; normotensive Wistar-Kyoto (WKY) control group. Vascular responses to KCl, noradrenaline (NA), endothelin-1 (ET-1), angiotensin II (Ang II), acetylcholine (ACh) and sodium nitroprusside (SNP) were tested on the femoral and renal artery. Left ventricle weight/body weight ratio (LVW/BW) was measured. Ang II and angiotensin-converting enzyme (ACE) activity in plasma and the left ventricle were determined. Plasma renin activity (PRA) was quantified. Results: Systolic blood pressure was decreased after nebivolol treatment in SHR. Compared with WKY, the contractions to KCl, NA, Ang II and ET-1 were increased in SHR while the relaxation to ACh was impaired. LVW/BW was higher in SHR. Levels of Ang II and ACE activity in plasma and the left ventricle were increased in SHR, but PRA was similar in these groups. Compared with atenolol, nebivolol markedly improved resistant vascular reactivity and decreased LVW/ BW and Ang II. But nebivolol had no influence on ACE activity and PRA in SHR. Conclusion: Nebivolol treatment improved resistant arterial reactivity and reduced left ventricular hypertrophy and Ang II in SHR.

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“…study, 15 a lower availability of plasma NO and lower levels of eNOS activity were found in both plasma and aorta samples from SHR. In the present study, both NEB and HCTZ administered alone were able to increase the mean plasma NO concentration significantly, compared with control SHR, NEB þ HCTZ did not provide greater bioavailability of plasma NO, and neither NEB nor HCTZ administered alone could increase the plasma NOS activity.…”

mentioning

confidence: 76%

“…19 NEB might counteract this mechanism by reducing peripheral resistance (as shown in other studies 30,31 ) and reducing the levels of asymmetric dimethylarginine that are increased during hypertension. 15 Mason et al 19 demonstrated that the preferential formation of highly reactive oxidative products (such as peroxynitrites) and the reduced bioavailability of NO, which is evident in endothelial cells of SHR, is restored by NEB treatment. In this context, it is interesting to note that HCTZ has also been shown to possess antioxidant properties in a model of renovascular hypertension, 32 therefore it can act in synergy with NEB in the eNOS uncoupling.…”

Section: Discussionmentioning

confidence: 99%

“…Tail systolic blood pressure (SBP), heart rate (HR) and water intake were measured at 0, 1, 2, 4 and 8 weeks after the beginning of therapy. Therapeutic doses were chosen on the basis of our previous experience with NEB monotherapy in SHR, 15 taking into account the ratio of NEB/HCTZ used in human hypertension research. 16 At the end of this study, animals were anaesthetized with 3% sodium pentobarbital via intraperitoneal injection (30 mg/ kg).…”

Section: Experimental Designmentioning

confidence: 99%

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Beneficial effects of nebivolol and hydrochlorothiazide combination in spontaneously hypertensive rats

2013

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The effect of nebivolol on asymmetric dimethylarginine system in spontaneously hypertension rats

Cited by 32 publications

References 30 publications

Probucol Protects Against Asymmetric Dimethylarginine-Induced Apoptosis in the Cultured Human Brain Microvascular Endothelial Cells

Probucol Protects Against Asymmetric Dimethylarginine-Induced Apoptosis in the Cultured Human Brain Microvascular Endothelial Cells

Nebivolol treatment improves resistant arterial function and reduces ventricular hypertrophy and angiotensin II in spontaneously hypertension rats

Beneficial effects of nebivolol and hydrochlorothiazide combination in spontaneously hypertensive rats

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