Resveratrol lowers blood pressure in spontaneously hypertensive rats via calcium-dependent endothelial NO production

Li, Xin; Dai, Yue; Yan, Shujun; Shi, Yanli; Li, Jing-Xiu; Liu, Jinglu; Cha, Li; Mu, Jianjun

doi:10.3109/10641963.2015.1089882

Cited by 25 publications

(20 citation statements)

References 35 publications

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“…Due to its natural and safe origin, the use of RESV has been reported in complications during pregnancy (22), including gestational diabetes mellitus (23). Of particular interest to our current study, the anti-hypertension property of RESV has also been demonstrated in a number of studies employing both animal and clinical studies (13, 14, 15, 16, 17). Given its widely reported anti-hypertensive function, we therefore also employed RESV in the current clinical trial among pregnant women affected by PE, with the hypothesis that RESV could also exhibit benefits in relieving hypertension in pregnancy-induced PE.…”

Section: Discussionmentioning

confidence: 85%

“…In a pregnant mouse model with reduced blood supply to the uterus, RESV increased uterine artery blood flow velocity and fetal weight (15). In spontaneously hypertensive rats, RESV could lower blood pressure through production of calcium-dependent endothelial NO (16). In addition, in a recent clinical trial among patients with primary hypertension, RESV was able to supplement standard anti-hypertensive therapy to effectively reduce blood pressure to normal levels (17).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia

Ding

Kang

Fan

et al. 2017

Endocrine Connections

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ObjectivePreeclampsia (PE) is a complication affecting pregnant women worldwide, which usually manifests as severe maternal hypertension. Resveratrol (RESV), a naturally existing polyphenol, is known to exhibit beneficial effects in cardiovascular disease including hypertension. We evaluated the outcome of treatment combining oral nifedipine (NIFE) and RESV against PE.Design and methodsUsing a randomized group assignment, 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo. Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis. Secondary endpoints were defined as the number of doses needed to control blood pressure, maternal and neonatal adverse effects.ResultsCompared with the NIFE + placebo group, the time needed to control blood pressure was significantly reduced in NIFE + RESV group, while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group. The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group. No differences in maternal or neonatal adverse effects were observed between the two treatment groups.ConclusionOur data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia

Ding

Kang

Fan

et al. 2017

Endocrine Connections

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“…This claim was backed up by reports of AMPK-dependent phosphorylation of eNOS (on Ser1177) following the exposure of cultured endothelial cells to agonists such as the vascular endothelial growth factor (VEGF) [ 9 ] and adiponectin [ 10 ], or pharmacological agents including peroxisome proliferator-activated receptor (PPAR) agonists [ 11 ] and statins [ 12 ]. Similar reports were also published using AMPK activators such as 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) [ 13 ] and metformin [ 14 , 15 ], or natural polyphenols like amurensin G [ 16 ] or resveratrol [ 17 ]. However, the effects are generally weak and much less impressive than the stimulation seen in response to hypoxia [ 7 ], shear stress [ 18 , 19 , 20 ], and thrombin [ 21 ] which result in robust AMPK activation.…”

Section: Introductionmentioning

confidence: 56%

Endothelial AMP-Activated Kinase α1 Phosphorylates eNOS on Thr495 and Decreases Endothelial NO Formation

Zippel

Loot

Stingl

et al. 2018

IJMS

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AMP-activated protein kinase (AMPK) is frequently reported to phosphorylate Ser1177 of the endothelial nitric-oxide synthase (eNOS), and therefore, is linked with a relaxing effect. However, previous studies failed to consistently demonstrate a major role for AMPK on eNOS-dependent relaxation. As AMPK also phosphorylates eNOS on the inhibitory Thr495 site, this study aimed to determine the role of AMPKα1 and α2 subunits in the regulation of NO-mediated vascular relaxation. Vascular reactivity to phenylephrine and acetylcholine was assessed in aortic and carotid artery segments from mice with global (AMPKα−/−) or endothelial-specific deletion (AMPKαΔEC) of the AMPKα subunits. In control and AMPKα1-depleted human umbilical vein endothelial cells, eNOS phosphorylation on Ser1177 and Thr495 was assessed after AMPK activation with thiopental or ionomycin. Global deletion of the AMPKα1 or α2 subunit in mice did not affect vascular reactivity. The endothelial-specific deletion of the AMPKα1 subunit attenuated phenylephrine-mediated contraction in an eNOS- and endothelium-dependent manner. In in vitro studies, activation of AMPK did not alter the phosphorylation of eNOS on Ser1177, but increased its phosphorylation on Thr495. Depletion of AMPKα1 in cultured human endothelial cells decreased Thr495 phosphorylation without affecting Ser1177 phosphorylation. The results of this study indicate that AMPKα1 targets the inhibitory phosphorylation Thr495 site in the calmodulin-binding domain of eNOS to attenuate basal NO production and phenylephrine-induced vasoconstriction.

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“…Resveratrol is an activator of SIRT1, which promotes expression and activity of eNOS to improve ACh‐mediated relaxation in rat aorta . Furthermore, in the isolated aorta of SHRs, resveratrol enhances ACh‐mediated relaxation ex vivo by increasing eNOS phosphorylation . Resveratrol treatment also enhances NO production in primary bovine aortic endothelial cells, while lowering blood pressure in SHRs after 4 weeks’ administration.…”

Section: Miscellaneous Agentsmentioning

confidence: 99%

Targeting the vascular dysfunction: Potential treatments for preeclampsia

et al. 2019

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Preeclampsia is a pregnancy-specific disorder clinically characterized by new-onset hypertension (>20 weeks' gestation) with one or more of proteinuria and maternal organ dysfunction such as renal insufficiency, liver dysfunction, neurological complications, fetal growth restriction, or uteroplacental dysfunction. 1,2 Each year, preeclampsia is the principal cause of death in over 60 000 women and in more than 500 000 babies globally. 3 The pathophysiological mechanisms underlying the disease are still not entirely clear. Briefly, In 2017, Sarah was awarded her PhD at the University of Melbourne, Australia, and is currently an NHMRC Peter Doherty Research Fellow in the Department of Obstetrics and Gynecology at Monash University, Australia. The focus of her research is to assess the potential of new and old therapeutics to target the vascular dysfunction of preeclampsia, and translate these studies into clinical application. AbstractPreeclampsia is a pregnancy-specific disorder, primarily characterized by new-onset hypertension in combination with a variety of other maternal or fetal signs. The pathophysiological mechanisms underlying the disease are still not entirely clear.Systemic maternal vascular dysfunction underlies the clinical features of preeclampsia. It is a result of oxidative stress and the actions of excessive anti-angiogenic factors, such as soluble fms-like tyrosine kinase, soluble endoglin, and activin A, released by a dysfunctional placenta. The vascular dysfunction then leads to impaired regulation and secretion of relaxation factors and an increase in sensitivity/production of constrictors. This results in a more constricted vasculature rather than the relaxed vasodilated state associated with normal pregnancy. Currently, the only effective "treatment" for preeclampsia is delivery of the placenta and therefore the baby.Often, this means a preterm delivery to save the life of the mother, with all the attendant risks and burdens associated with fetal prematurity. To lessen this burden, there is a pressing need for more effective treatments that target the maternal vascular dysfunction that underlies the hypertension. This review details the vascular effects of key drugs undergoing clinical assessment as potential treatments for women with preeclampsia.

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Resveratrol lowers blood pressure in spontaneously hypertensive rats via calcium-dependent endothelial NO production

Abstract: Resveratrol increases endothelial NO production to improve endothelial dysfunction and lowers BP in hypertensive rats, which depends on calcium-eNOS activation.

Cited by 25 publications

References 35 publications

Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia

Efficacy of resveratrol to supplement oral nifedipine treatment in pregnancy-induced preeclampsia

Endothelial AMP-Activated Kinase α1 Phosphorylates eNOS on Thr495 and Decreases Endothelial NO Formation

Targeting the vascular dysfunction: Potential treatments for preeclampsia

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