Abstract：
:Patients with obstructive sleep apnea (OSA) have a high prevalence of atrial fibrillation (AF). Rivaroxaban, a coagulation factor Xa inhibitor, has recently been reported to show pleiotropic effects. This study investigated the influence of rivaroxaban on cardiac remodeling caused by intermittent hypoxia (IH). Male C57BL/6J mice were exposed to IH (repeated cycles of 5% oxygen for 1.5 min followed by 21% oxygen for 5 min) for 28 days with/without rivaroxaban (12 mg/kg/day) or FSLLRY, a protease-activated receptor (PAR)-2 antagonist (10 μg/kg/day). IH caused endothelial cell degeneration in the small arteries of the right atrial myocardium and increased the level of %fibrosis and 4-hydroxy-2-nonenal protein adducts in the left ventricular myocardium. IH also increased the expression of PAR-2 as well as the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and nuclear factor-kappa B (NF-κB) were increased in human cardiac microvascular endothelial cells. However, rivaroxaban and FSLLRY significantly suppressed these changes. These findings demonstrate that rivaroxaban attenuates both atrial and ventricular remodeling induced by IH through the prevention of oxidative stress and fibrosis by suppressing the activation of ERK and NF-κB pathways via PAR-2. Treatment with rivaroxaban could potentially become a novel therapeutic strategy for cardiac remodeling in patients with OSA and AF.
journal_name
J Pharmacol Scijournal_title
Journal of pharmacological sciencesauthors
Imano H,Kato R,Tanikawa S,Yoshimura F,Nomura A,Ijiri Y,Yamaguchi T,Izumi Y,Yoshiyama M,Hayashi Tdoi
10.1016/j.jphs.2018.07.002subject
Has Abstractpub_date
2018-07-01 00:00:00pages
274-282issue
3eissn
1347-8613issn
1347-8648pii
S1347-8613(18)30116-6journal_volume
137pub_type
杂志文章abstract：:A segment of guinea pig ileum was used to confirm the hypothesis that [6]-gingerol and lafutidine interact with capsaicin-sensitive neurons. Addition of 30 and 100 microM [6]-gingerol (a pungent constituent of ginger) induced contraction of the ileum immediately. Like capsaicin, [6]-gingerol-induced contraction was in...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.92.359
更新日期：2003-08-01 00:00:00
abstract：:Lamotrigine (LTG) is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder and it has been known that LTG targets voltage-dependent sodium channels (VGSCs). In this study, we investigated the effect of LTG on the Nav1.4 Na(+) current using HEK293 cells expressing mouse Nav1.4 VGSCs. By the trea...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.13116sc
更新日期：2013-01-01 00:00:00
abstract：:Luminal hydrogen sulfide (H(2)S), a gasotransmitter, causes colonic pain / referred hyperalgesia in mice, most probably via activation of T-type Ca(2+) channels. Here we analyzed the mechanisms for H(2)S-induced facilitation of colonic pain signals. Intracolonic administration of NaHS, an H(2)S donor, evoked visceral ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.12086sc
更新日期：2012-01-01 00:00:00
abstract：:Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcriptional factor implicated in regulating adipogenesis, glucose homeostasis, and in mediating the action of the insulin sensitizing anti-diabetic thiazolidinedione (TZD) compounds. [3-(2,4-Dichlorobenzyl)-2-methyl-N-(pentylsulfony...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0050578
更新日期：2005-12-01 00:00:00
abstract：:Genetically epilepsy-prone rats (GEPR-9s) were derived from Sprague-Dawley rats (SD). The number of kainate-induced wet dog shake behavior (WDS) responses was found to decrease significantly in GEPR-9s compared to SD. WDS responses were potentiated by 5-hydroxytryptophan or 2,5-dimethoxy-4-iodoamphetamine and antagoni...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.09015sc
更新日期：2009-07-01 00:00:00
abstract：:The aim of this study was to investigate the contribution of gene polymorphisms, in combination with habitual caffeine consumption, to the effect of caffeine intake on hemodynamic and psychoactive parameters. A double-blind, prospective study was conducted with 201 healthy volunteers randomly allocated 2:1 to the caff...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.jphs.2019.01.006
更新日期：2019-03-01 00:00:00
abstract：:The critical role played by the renin-angiotensin-aldosterone system (RAAS) in the regulation of blood pressure and body fluid homeostasis has been well recognized. Angiotensin (Ang) II and aldosterone are the most powerful biologically active products of the RAAS, although there are also other bioactive Ang peptides ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.10r03fm
更新日期：2010-01-01 00:00:00
abstract：:Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily) inhibited the development of mechanical allodynia induced by paclitaxel (4 mg...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2016.04.019
更新日期：2016-06-01 00:00:00
abstract：:In the present study, the characteristics of the sleep features of amitriptyline, mexiletine, and N-(4-tertiarybutylphenyl)-4-(3-cholorphyridin-2-yl)tetrahydropyradine-1(2H)-carbox-amide (BCTC) were studied. Electrodes were chronically implanted into the frontal cortex and the dorsal neck muscles of rats for electroen...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.08059fp
更新日期：2008-07-01 00:00:00
abstract：:MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate translational repression of multiple target mRNAs. The miRNAs in a whole cell regulate greater than 30% of all protein-coding genes. The vast majority of presently identified miRNAs are expressed in the brain in a spatially and temporally controlled ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.10r11fm
更新日期：2010-01-01 00:00:00
abstract：:Pulmonary arterial hypertension (PAH) is defined as elevation of mean pulmonary arterial pressure to ≥25 mmHg within the low pressure pulmonary circulatory system. PAH is characterized by obstructive vascular remodeling, partially due to excessive pulmonary arterial smooth muscle cell (PASMC) proliferation. Puerarin i...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2019.09.010
更新日期：2019-10-01 00:00:00
abstract：:This study investigated the effects of thiol and heme oxidants on responsiveness to cGMP generators in isolated rat aorta and pulmonary artery using an organ chamber. The nitric oxide (NO) donor sodium nitroprusside (SNP)-induced relaxation was impaired by exposure to the thiol oxidant diamide in both the aorta and th...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2019.04.002
更新日期：2019-05-01 00:00:00
abstract：:The cell signaling cascades provoked by Wnt proteins (the Wnt signaling pathways), which are well conserved through evolution, play crucial roles to maintain homeostasis of a variety of tissues such as skin, blood, intestine, and brain, as well as to regulate proliferation, morphology, motility, and fate of cells duri...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.cr0070024
更新日期：2007-08-01 00:00:00
abstract：:The distribution of group I metabotropic glutamate receptors in rat hippocampal cells in culture was examined by calcium imaging and immunocytochemistry. To distinguish different cell types in the culture, the effects of t-ACPD ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid) and of NMDA (N-methyl-D-aspartate) were...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.92.245
更新日期：2003-07-01 00:00:00
abstract：:Yeasts isolated from patients with superficial mycoses were tested against propolis samples collected from different regions and honeybee races. The minimum inhibitory concentration (MIC) values obtained using the agar dilution methods were compared to the diameters of growth inhibition zones by using the disk diffusi...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fpe05002x
更新日期：2005-09-01 00:00:00
abstract：:Disruption of the blood-brain barrier (BBB) has been considered as a major pathological change in stroke. eNOS/NO play a key role in maintain BBB function. Myricetin is one of the common flavones widely exists in food and fruit, show certain protective effect on the brain function. This experiment establishes oxygeneg...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2019.04.009
更新日期：2019-05-01 00:00:00
abstract：:In the present study, we investigated whether a novel benzopyranylindol analogue, KR-31466 (KR466) (1-[(2S,3R,4S)-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-6-nitro-2H-1-benzopyran-4-yl]-1H-indole-2-carboxylic acid ethyl ester) can attenuate hypoxic injury in heart-derived H9c2 cells and, if so, whether the prot...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.92.13
更新日期：2003-05-01 00:00:00
abstract：:Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. This combination appears to produce synergistic effects on behavior at low doses; however, there is little direct evidence that the combination is stronger than either drug alone. Therefore, we investigated interaction...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fpj04039x
更新日期：2004-12-01 00:00:00
abstract：:Sneezing and persistent itching of the nasal mucosa are distressing symptoms of allergic rhinitis (AR). Recent studies have revealed that hyperinnervation of sensory neurons in the nasal turbinate is one of the underlying causes of sneezing and itching. Since Semaphorin-3A (Sema3A) has been previously shown to restric...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.11005fp
更新日期：2011-01-01 00:00:00
abstract：:The supraspinal and spinal antinociceptive effects of several kappa-opioid receptor agonists were examined in diabetic and non-diabetic mice using the tail-flick assay. The antinociception induced by intrathecal (i.t.), but not intracerebroventricular (i.c.v.), CI-977, a highly selective kappa(1)-opioid receptor agoni...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0040621
更新日期：2005-05-01 00:00:00
abstract：:Boron neutron capture therapy (BNCT) is a radiotherapy utilizing the neutron capture and nuclear fission reaction of 10B taken up into tumor cells. The most commonly used boron agent in BNCT, p-borono-l-phenylalanine (BPA), is accumulated in tumors by amino acid transporters upregulated in tumor cells. Here, by using ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2019.01.012
更新日期：2019-03-01 00:00:00
abstract：:Bee venom (BV) has been used in patients with rheumatoid arthritis, a condition characterized by rheumatoid joint destruction mediated, in large part, by matrix metalloproteinases (MMPs). We investigated the effects of melittin, a major component of bee venom, on the production of MMPs in human rheumatoid arthritic fi...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.sc0070215
更新日期：2008-01-01 00:00:00
abstract：:Kursi Wufarikun Ziyabit (KWZ) is a traditional prescription that used in folk tea drinking for its health care effect in treatment of type 2 diabetes mellitus (T2DM) in central Asia. However, the underlying mechanism of KWZ in T2DM has not been investigated extensively. This study designed to observe the effect of KWZ...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2018.06.011
更新日期：2018-06-01 00:00:00
abstract：:The possible role of nitric oxide (NO) in anxiety following transient cerebral ischemia by a 10-min bilateral carotid occlusion was examined in mice. Two days after the ischemia, mice showed a significant decrease in time spent on the open arms in the elevated plus-maze test; and likewise, they showed shortened social...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.91.47
更新日期：2003-01-01 00:00:00
abstract：:We have developed an in vivo mouse model [the green fluorescent protein (GFP) / carbon tetrachloride (CCl(4)) model] and reported that infused GFP-positive bone marrow cells administered via a tail vein efficiently repopulated cirrhotic liver tissue under conditions of persistent liver damage induced by CCl(4). Moreov...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.10r13fm
更新日期：2011-01-01 00:00:00
abstract：:Aristolochic acids (AAs), contained in Chinese herbal preparations, have been considered to induce nephropathy. In order to elucidate the molecular mechanisms of AA-induced nephrotoxicity, we have elucidated the interaction of human organic anion transporters (hOATs) with AAs using their stable cell lines. AA-I and AA...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.09339sc
更新日期：2010-01-01 00:00:00
abstract：:Alzheimer's disease (AD) is the most common neurodegenerative disorder of late life characterized by insidious, chronic, and progressive memory impairment in association with the accumulation of senile plaques, neurofibrillary tangles, and massive loss of neurons. Apoptosis is believed to be an important contributor t...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章,评审
doi：10.1254/jphs.cpj04006x
更新日期：2005-03-01 00:00:00
abstract：:Resveratrol is a stilbene compound found in grapes and other sources. In this study we examined the effects of trans-resveratrol (4.38 - 438 microM/implant) in the vasculogenesis of yolk-sac membranes and its capacity to improve chick embryo growth. High concentrations of the stilbene (43.8 - 438 microM) significantly...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.fp0071876
更新日期：2008-06-01 00:00:00
abstract：:The role of nitric oxide (NO) on intestinal mucosal injury induced by single or consecutive administration of methotrexate was investigated in a rodent model. Rats received methotrexate intraperitoneally either as a single administration (50 mg/kg) or as a consecutive administration (12.5 mg/kg/day) for 4 days. NG-nit...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1016/j.jphs.2020.02.006
更新日期：2020-05-01 00:00:00
abstract：:Glucocorticoids are stress hormones released from the adrenal cortex and their concentration is controlled by the hypothalamic-pituitary-adrenal axis. In this study, we investigated the effect of glucocorticoids on the number of astrocytes and glucocorticoid receptor (GR) expression in vitro and in vivo. Proliferation...
journal_title：Journal of pharmacological sciences
pub_type： 杂志文章
doi：10.1254/jphs.12047fp
更新日期：2012-01-01 00:00:00
