Magnesium Sulfate–Mediated Vascular Relaxation and Calcium Channel Activity in Placental Vessels Different From Nonplacental Vessels

Tang, Jiaqi; He, Axin; Li, Na; Chen, Xueyi; Zhou, Xiuwen; Fan, Xiaoning; Liu, Yanping; Zhang, Mengshu; Qi, Linglu; Tao, Jianying; Sun, Miao; Xu, Zhice

doi:10.1161/jaha.118.009896

Cited by 17 publications

(8 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was anticipated that hypermagnesemia will increase Mg 2+ concentration in the CSF, but no changes were noted, which was surprising considering the high plasma Mg 2+ concentrations achieved. As Mg 2+ serves as a natural Ca 2+ channel blocker (Houston, 2011; Tang et al., 2018), in addition to its peripheral effect on small vessels, we speculated that its calming effects could be mediated by blocking central NMDA receptors and voltage‐dependent calcium channels. However, the lack of changes in CSF electrolyte concentration makes this mechanism less likely.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

Schumacher

Toribio

Scansen

et al. 2020

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

The objectives of this study were to describe pharmacokinetic and pharmacodynamic changes as a result of a single intravenous administration of magnesium sulfate (MgSO4) to healthy horses. MgSO4 is a magnesium salt that has been used to calm horses in equestrian competition and is difficult to regulate because magnesium is an essential constituent of all mammals. Six healthy adult female horses were administered a single intravenous dose of MgSO4 at 60 mg/kg of body weight over 5 min. Blood, urine, and cerebrospinal fluid (CSF) samples were collected, and cardiovascular parameters were monitored and echocardiograms performed at predetermined times. Noncompartmental pharmacokinetic analysis was applied to plasma concentrations of ionized magnesium (Mg2+). Objective data were analyzed using the Wilcoxon rank‐sum test with p < .05 used as a determination for significance. Plasma concentrations of Mg2+ increased nearly fivefold, ionized calcium (Ca2+) decreased by nearly 10%, and the Ca2+ to Mg2+ ratio declined more than 3.5‐fold and remained different than baseline until 24 hr (p < .05). Significant changes were seen with urinary fractional excretion of electrolytes, cardiovascular parameters, and echocardiographic measurements. No changes were detected in CSF electrolyte concentrations. The decrease in Ca2+ result of hypermagnesemia supports the interaction between these cations. Alterations detected in plasma electrolyte concentrations and urinary fractional excretion of electrolytes may serve as biomarkers for regulatory control for the nefarious administration of MgSO4.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

Schumacher

Toribio

Scansen

et al. 2020

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

show abstract

“…7a, b). Both MgSO 4 and corticosteroids are known to relax the vasculature 73,74 . However, it is unclear whether vasodilation or other responses invoked by MgSO 4 and/or BMTZ confer neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor

et al. 2020

View full text Add to dashboard Cite

Prematurity is associated with perinatal neuroinflammation and injury. Screening for genetic modulators in an LPS murine model of preterm birth revealed the upregulation of Nr4a1, an orphan nuclear transcription factor that is normally absent or limited in embryonic brains. Concurrently, Nr4a1 was downregulated with magnesium sulfate (MgSO 4) and betamethasone (BMTZ) treatments administered to LPS exposed dams. To understand the role of Nr4a1 in perinatal brain injury, we compared the preterm neuroinflammatory response in Nr4a1 knockout (KO) versus wild type (wt) mice. Key inflammatory factors Il1b, Il6 and Tnf, and Iba1+ microglia were significantly lower in Nr4a1 KO versus wt brains exposed to LPS in utero. Treatment with MgSO 4 /BMTZ mitigated the neuroinflammatory process in wt but not Nr4a1 KO brains. These results correspond with a reduction in cerebral hemorrhage in wt but not mutant embryos from dams given MgSO 4 /BMTZ. Further analysis with Nr4a1-GFP-Cre × tdTomato loxP reporter mice revealed that the upregulation of Nr4a1 with perinatal neuroinflammation occurs in the cerebral vasculature. Altogether, this study implicates Nr4a1 in the developing vasculature as a potent mediator of neuroinflammatory brain injury that occurs with preterm birth. It is also possible that MgSO 4 /BMTZ mitigates this process by direct or indirect inhibition of Nr4a1.

show abstract

“…Placental vessels were characterised by much weaker responses to MgSO 4 -mediated vasodilatation compared with non-placental vessels. 46 Thus, our study reports for the first time that CACNA1D mutations may cause pre-eclampsia.…”

Section: Discussionmentioning

confidence: 55%

Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting

Bao

et al. 2020

J Med Genet

View full text Add to dashboard Cite

BackgroundMonogenic hypertension describe a series of hypertensive syndromes that are inherited by Mendelian laws. Sometimes genetic testing is required to provide evidence for their diagnoses, precise classification and targeted treatment. This study is the first to investigate the clinical utility of a causative gene screening and the combined yield of gene product expression analyses in cases with suspected monogenic hypertension.MethodsWe performed a large-scale multi-centre clinical genetic research of 1179 expertly selected hypertensive individuals from the Chinese Han population. Targeted sequencing were performed to evaluate 37 causative genes of potential cases of monogenic hypertension. Pathogenic and likely pathogenic variants were classified using the American College of Medical Genetics guidelines. Additionally, 49 variants of unknown significance (VUS) that had relatively high pathogenicity were selected and analysed using immunoblot protein expression assays.Results21 pathogenic or likely pathogenic variants were identified in 33 of 1179 cases (2.80%). Gene product expression analyses showed 27 VUSs harboured by 49 individuals (4.16%) could lead to abnormally expressed protein levels. Consequently, combining genetic screening with gene product expression analyses increased the diagnostic yield from 2.80% to 6.79%. The main aetiologies established were primary aldosteronism (PA; 27, 2.29%) and pheochromocytoma and paraganglioma (PPGL; 10, 0.85%).ConclusionMolecular diagnoses obtained using causative gene screening combined with gene product expression analyses initially achieved a modest diagnostic yield. Our data highlight the predominant roles of PA and PPGL. Furthermore, we provide evidence indicating the enhanced diagnostic ability of combined genetic and functional evaluation.

show abstract

Magnesium Sulfate–Mediated Vascular Relaxation and Calcium Channel Activity in Placental Vessels Different From Nonplacental Vessels

Cited by 17 publications

References 26 publications

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

Pharmacokinetics of magnesium and its effects on clinical variables following experimentally induced hypermagnesemia

The orphan nuclear receptor Nr4a1 mediates perinatal neuroinflammation in a murine model of preterm labor

Genetic screening for monogenic hypertension in hypertensive individuals in a clinical setting

Contact Info

Product

Resources

About