Effects of atorvastatin, amlodipine, and their combination on vascular dysfunction in insulin-resistant rats.

Abstract:

:Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O2(-)) generation in the insulin-resistant state. We investigated the effects of atorvastatin, a 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor; amlodipine, a calcium antagonist; and their combination on blood pressure, arterial relaxation and contraction, and vascular oxidative stress in aortas of high fructose-fed rats. Oral administration of atorvastatin for 8 weeks did not significantly lower blood pressure, but normalized angiotensin II-induced vasoconstriction and endothelial function in the fructose-fed rats. Atorvastatin treatment of fructose-fed rats increased vascular BH4 content, which was associated with an increase in endothelial NO synthase activity as well as a reduction in endothelial O2(-) production. On the other hand, administration of amlodipine did not affect the angiotensin II-induced vasoconstriction and endothelial function, but normalized the elevated blood pressure in the fructose-fed rats. The combined treatment did not show synergistic but additive beneficial effects. The present study suggests that combined therapy of HMG-CoA reductase inhibitors and calcium antagonists prevents functional vascular disorders in the insulin-resistant state, possibly resulting in the protection against or delay of development of hypertension, vascular dysfunction in diabetes, and thereafter atherosclerosis.

journal_name

J Pharmacol Sci

authors

Okamura T,Tawa M,Geddawy A,Shimosato T,Iwasaki H,Shintaku H,Yoshida Y,Masada M,Shinozaki K,Imamura T

doi

10.1254/jphs.13178fp

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

76-85

issue

1

eissn

1347-8613

issn

1347-8648

pii

DN/JST.JSTAGE/jphs/13178FP

journal_volume

124

pub_type

杂志文章
  • History of the G protein-coupled receptor (GPCR) assays from traditional to a state-of-the-art biosensor assay.

    abstract::The G protein-coupled receptors (GPCRs) form the largest and the most versatile superfamily that share a seven-transmembrane-spanning architecture. GPCR-signaling is involved in vision, taste, olfaction, sympathetic/parasympathetic nervous functions, metabolism, and immune regulation, indicating that GPCRs are extreme...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1254/jphs.14R13CP

    authors: Miyano K,Sudo Y,Yokoyama A,Hisaoka-Nakashima K,Morioka N,Takebayashi M,Nakata Y,Higami Y,Uezono Y

    更新日期:2014-01-01 00:00:00

  • Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects.

    abstract::Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in h...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2015.01.003

    authors: Noguchi K,Matsuzaki T,Sakanashi M,Hamadate N,Uchida T,Kina-Tanada M,Kubota H,Nakasone J,Sakanashi M,Ueda S,Masuzaki H,Ishiuchi S,Ohya Y,Tsutsui M

    更新日期:2015-02-01 00:00:00

  • Contrasting dose-effects of multi-glycoside of Tripterygium wilfordii HOOK. f. on glomerular inflammation and hepatic damage in two types of anti-Thy1.1 glomerulonephritis.

    abstract::Multi-glycoside, one of the extracted compounds from Tripterygium wilfordii HOOK. f. (GTW), has been shown to be clinically effective in suppressing glomerular inflammation in chronic kidney disease. However, its clinical application is often limited by its cytotoxic actions on the liver. This study was performed to c...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.11157fp

    authors: Wan YG,Zhao Q,Sun W,Zhang HL,Li M,Wei QX,Wu W,Yue LJ,Wang Q

    更新日期:2012-01-01 00:00:00

  • Vanadate activates Rho A translocation in association with contracting effects in ileal longitudinal smooth muscle of guinea pig.

    abstract::We characterized the effects of vanadate, an inhibitor of tyrosine phosphatase, on the tension, the level of myosin light chain (MLC) phosphorylation, and Rho A activation in intact ileal longitudinal smooth muscle of the guinea pig to study the role of tyrosine phosphorylation in contraction signaling. Vanadate exert...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.fp0030576

    authors: Mori M,Tsushima H

    更新日期:2004-08-01 00:00:00

  • Myricetin ameliorated ischemia/reperfusion-induced brain endothelial permeability by improvement of eNOS uncoupling and activation eNOS/NO.

    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

    authors: Zhang S,Hu X,Guo S,Shi L,He Q,Zhang P,Yu S,Zhao R

    更新日期:2019-05-01 00:00:00

  • A comparative pharmacology study between the intracolonic and oral routes of 5-FU administration in a colon cancer-bearing Yoshida sarcoma rat model.

    abstract::We prepared a colon cancer-bearing Yoshida sarcoma rat model to examine the dose-response relationship of antitumor activity of intracolonically or orally administered 5-fluorouracil (5-FU; 45, 30, 20, 13, and 8 mg/kg). At doses of > or =20 mg/kg and > or =30 mg/kg, the 5-FU intracolonic and oral administration groups...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.fp0040139

    authors: Goto T,Tomizawa N,Kobayashi E,Fujimura A

    更新日期:2004-06-01 00:00:00

  • Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, induces human hepatocellular carcinoma cell apoptosis via ROS/MAPKs dependent mitochondrial pathway.

    abstract::Calf Spleen Extractive Injection (CSEI), a small peptides enriched extraction, performs immunomodulatory activity on cancer patients suffering from radiotherapy or chemotherapy. The present study aims to investigate the anti-hepatocellular carcinoma effects of CSEI in cells and tumor-xenografted mouse models. In HepG2...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2016.08.006

    authors: Jia D,Lu W,Zhang X,Cai G,Teng L,Wang X,Zhang M,Zeng Y,Liang C,Wang D

    更新日期:2016-10-01 00:00:00

  • Lack of enhanced effect of antipsychotics combined with fluvoxamine on acetylcholine release in rat prefrontal cortex.

    abstract::We have shown that coadministration of sulpiride and fluvoxamine preferentially increases the release of dopamine in the prefrontal cortex. To study the possible role of the cortical cholinergic system in this effect, we combined several other antipsychotic drugs with fluvoxamine and examined the effects on acetylchol...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.sc0060187

    authors: Ago Y,Sato M,Nakamura S,Baba A,Matsuda T

    更新日期:2006-12-01 00:00:00

  • How do acupuncture and moxibustion act? - Focusing on the progress in Japanese acupuncture research -.

    abstract::The mechanisms of action of acupuncture and moxibustion as reported by Japanese researchers are reviewed. The endogenous opioid-mediated mechanisms of electroacupuncture (EA) as used in China are well understood, but these are only one component of all mechanisms of acupuncture. These studies emphasize the similarity ...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1254/jphs.crj06004x

    authors: Kawakita K,Shinbara H,Imai K,Fukuda F,Yano T,Kuriyama K

    更新日期:2006-01-01 00:00:00

  • Blonanserin extensively occupies rat dopamine D3 receptors at antipsychotic dose range.

    abstract::Antagonism of the dopamine D3 receptor has been hypothesized to be beneficial for schizophrenia cognitive deficits, negative symptoms and extrapyramidal symptoms. However, recent animal and human studies have shown that most antipsychotics do not occupy D3 receptors in vivo, despite their considerable binding affinity...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2015.01.007

    authors: Baba S,Enomoto T,Horisawa T,Hashimoto T,Ono M

    更新日期:2015-03-01 00:00:00

  • Dentin hypersensitivity-like tooth pain seen in patients receiving steroid therapy: An exploratory study.

    abstract::To ascertain whether steroid therapy evokes dentin hypersensitivity (DH)-like tooth pain, we performed a study based on compelling evidence from patients receiving steroid therapy. An exploratory study was conducted using a questionnaire for 220 patients prescribed steroids who attended the Department of Hematology an...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2016.10.004

    authors: Shoji N,Endo Y,Iikubo M,Ishii T,Harigae H,Aida J,Sakamoto M,Sasano T

    更新日期:2016-11-01 00:00:00

  • Regulation of ryanodine receptor-mediated Ca(2+) release in vas deferens smooth muscle cells.

    abstract::Ca(2+) release from intracellular store sites via the ryanodine receptor (RyR) and hormonal regulation by flutamide, an androgen-receptor (AR) antagonist, on it were examined in vas deferens (VD) smooth muscle cells (SMCs). VD and VDSMCs were obtained from two groups of male rats that were treated p.o. with 100 mg/kg ...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.09037fp

    authors: Ohno A,Ohya S,Yamamura H,Imaizumi Y

    更新日期:2009-05-01 00:00:00

  • Involvement of histamine released from mast cells in acute radiation dermatitis in mice.

    abstract::A possible involvement of histamine in acute radiation dermatitis in mice was investigated. The dose of 40 Gy of gamma irradiation induced erythema and edema in C57BL/6 mice treated with vehicle. However, in C57BL/6 mice treated with chlorpheniramine and WBB6F1-W/Wv mice, erythema and edema were not observed. In all o...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.sc0070127

    authors: Moriyasu S,Yamamoto K,Kureyama N,Okamura K,Ikeda T,Yamatodani A

    更新日期:2007-06-01 00:00:00

  • A receptor-independent effect of estrone sulfate on the HERG channel.

    abstract::We recently reported that physiological concentrations of 17beta-estradiol partially down-regulate cardiac rapidly-activating delayed rectifier K(+) currents (hERG currents) independently of estrogen-receptor signaling. To determine if other estrogens have the same effect as that of 17beta-estradiol, we investigated r...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.08257sc

    authors: Kakusaka S,Asayama M,Kaihara A,Sasano T,Suzuki T,Kurokawa J,Furukawa T

    更新日期:2009-01-01 00:00:00

  • Neuroprotective DAMPs member prothymosin alpha has additional beneficial actions against cerebral ischemia-induced vascular damages.

    abstract::Prothymosin alpha (ProTα) suppresses stress-induced necrosis of cultured cortical neurons. As neuroprotection alone could not explain the long-lasting protective actions against cerebral ischemia by ProTα, we further examined whether ProTα, in addition to neuroprotective effects, has other anti-ischemic activities. Wh...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2016.05.006

    authors: Maeda S,Sasaki K,Halder SK,Fujita W,Ueda H

    更新日期:2016-09-01 00:00:00

  • FK614, a novel peroxisome proliferator-activated receptor gamma modulator, induces differential transactivation through a unique ligand-specific interaction with transcriptional coactivators.

    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

    authors: Fujimura T,Sakuma H,Konishi S,Oe T,Hosogai N,Kimura C,Aramori I,Mutoh S

    更新日期:2005-12-01 00:00:00

  • New methods to evaluate endothelial function: A search for a marker of nitric oxide (NO) in vivo: re-evaluation of NOx in plasma and red blood cells and a trial to detect nitrosothiols.

    abstract::Although plasma NOx (NO(2)(-) and NO(3)(-)) has been used as an index of nitric oxide (NO) formation in vivo, many unreasonable results appeared even after active elimination of NOx contamination from laboratory ware. For example, plasma NOx concentrations did not increase during vasodilation mediated by the NO/cGMP p...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1254/jphs.93.409

    authors: Ishibashi T,Yoshida J,Nishio M

    更新日期:2003-12-01 00:00:00

  • Effect of lamotrigine on Na(v)1.4 voltage-gated sodium channels.

    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

    authors: Nakatani Y,Masuko H,Amano T

    更新日期:2013-01-01 00:00:00

  • Microminipig, a non-rodent experimental animal optimized for life science research:novel atherosclerosis model induced by high fat and cholesterol diet.

    abstract::Atherosclerotic lesions were observed in male and ovariectomized female Microminipig (MMP) fed a high fat and cholesterol diet with sodium cholate (HFCD/SC) for 3 months. HFCD/SC induced hypercholesterolemia accompanied by an increase in serum total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), hig...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1254/jphs.10r17fm

    authors: Kawaguchi H,Miyoshi N,Miura N,Fujiki M,Horiuchi M,Izumi Y,Miyajima H,Nagata R,Misumi K,Takeuchi T,Tanimoto A,Yoshida H

    更新日期:2011-01-01 00:00:00

  • Entecavir as a P2X7R antagonist ameliorates platelet activation and thrombus formation.

    abstract::Platelet activation is the primary cause of thrombosis. The P2X7 receptor (P2X7R) is a therapeutic target of thrombosis. However, it is still unknown whether P2X7R activation affects platelet thrombus. Our molecular docking results showed that entecavir as a P2X7R antagonist interacted perfectly with the human P2X7R (...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2020.07.002

    authors: Ming Y,Xin G,Ji B,Ji C,Wei Z,Zhang B,Zhang J,Yu K,Zhang X,Li S,Li Y,Xing Z,Niu H,Huang W

    更新日期:2020-09-01 00:00:00

  • Protective effects of pioglitazone against global cerebral ischemic-reperfusion injury in gerbils.

    abstract::Despite of the huge socio-economic burden, stroke still represents an unmet therapeutic need. Researchers failed to reproduce preclinical efficacy in subsequent clinical development. To bridge this translation failure, the Stroke Therapy Academic Industry Round Table (STAIR) has suggested a rigorous, robust, and detai...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.08246fp

    authors: Kaundal RK,Iyer S,Kumar A,Sharma SS

    更新日期:2009-03-01 00:00:00

  • 4-Chlorophenylguanidine is an ASIC3 agonist and positive allosteric modulator.

    abstract::Acid-sensing ion channels (ASICs) are proton-sensitive sodium channels that open in response to lowered extracellular pH and are expressed in the central and peripheral nervous systems. The ASIC3 subtype is found primarily in the periphery where the channel mediates pain signals caused by ischemia and inflammation. He...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2017.02.007

    authors: Agharkar AS,Gonzales EB

    更新日期:2017-03-01 00:00:00

  • Novel findings for the development of drug therapy for various liver diseases: Current state and future prospects for our liver regeneration therapy using autologous bone marrow cells for decompensated liver cirrhosis patients.

    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

    authors: Takami T,Terai S,Sakaida I

    更新日期:2011-01-01 00:00:00

  • Possible involvement of β₁ receptors in various emetogen-induced increases in salivary amylase activity in rats.

    abstract::We investigated the inhibitory effects of β₁- or β₂-adrenoceptor (AR) antagonists on salivary amylase secretion produced by various emetic agents, such as cisplatin, apomorphine, and lithium chloride (LiCl), or the non-emetic agent β(½)-AR agonist isoprenaline in rats. We also determined the inhibitory effect of metoc...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.10265fp

    authors: Fukui H,Suyama Y,Iwachido T,Miwa E

    更新日期:2011-01-01 00:00:00

  • Calmodulin- and Ca2+-dependent facilitation and inactivation of the Cav1.2 Ca2+ channels in guinea-pig ventricular myocytes.

    abstract::The L-type Ca(2+) channel (Ca(V)1.2) shows clear Ca(2+)-dependent facilitation and inactivation. Here we have examined the effects of calmodulin (CaM) and Ca(2+) on Ca(2+) channel in guinea-pig ventricular myocytes in the inside-out patch mode, where rundown of the channels was controlled. At a free [Ca(2+)] of 0.1 mi...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.09282fp

    authors: Han DY,Minobe E,Wang WY,Guo F,Xu JJ,Hao LY,Kameyama M

    更新日期:2010-01-01 00:00:00

  • Pharmacology in health foods: effects of arachidonic acid and docosahexaenoic acid on the age-related decline in brain and cardiovascular system function.

    abstract::Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are major constituents of cell membranes and play important roles in preserving physiological and psychological function. Recently, data from several studies have indicated that impairments in long-term potentiation (LTP), the process underlying plasticity in synap...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章,评审

    doi:10.1254/jphs.10r39fm

    authors: Kiso Y

    更新日期:2011-01-01 00:00:00

  • Chronopharmacology of angiotensin II-receptor blockers in stroke-prone spontaneously hypertensive rats.

    abstract::Protective effect of valsartan (Val), an angiotensin II (AII)-receptor blocker (ARB), against organ damage is reported to depend on the dosing time in hypertensive patients. Dosing-time-dependent effect of Val on survival of stroke-prone spontaneously hypertensive rats (SHRSP) under a 12-h lighting cycle was examined....

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.10284fp

    authors: Liu Y,Ushijima K,Ohmori M,Takada M,Tateishi M,Ando H,Fujimura A

    更新日期:2011-01-01 00:00:00

  • Chronic treatment with imipramine inhibits cell growth and enhances serotonin 2C receptor mRNA expression in NG 108-15 cells.

    abstract::We previously reported that NG108-15 cells contain intrinsic serotonin 2C receptor (5-HT2CR). The effects of imipramine, a 5-HT2CR antagonist, on cell growth, cell viability, and the 5-HT2CR mRNA level were investigated in this study. Repeated treatment with imipramine at concentrations of 1 - 10 microM for 5 days inh...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.92.433

    authors: Sukma M,Tohda M,Watanabe H

    更新日期:2003-08-01 00:00:00

  • Cucurbitacin B induces inhibitory effects via the CIP2A/PP2A/C-KIT signaling axis in t(8;21) acute myeloid leukemia.

    abstract::Acute myeloid leukemia (AML) is the most common subtype of hematological malignancy in humans, and its incidence increases with age. The treatment of AML still faces challenges. Therefore, there is an urgent need to develop more effective targeted therapies. The receptor tyrosine kinase C-KIT confers critical prolifer...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1016/j.jphs.2018.12.010

    authors: Ma W,Xiang Y,Yang R,Zhang T,Xu J,Wu Y,Liu X,Xiang K,Zhao H,Liu Y,Si Y

    更新日期:2019-04-01 00:00:00

  • Hemostatic action of OC-108, a novel agent for hemorrhoids, is associated with regional blood flow arrest induced by acute inflammation.

    abstract::Clinically, hemorrhoidal bleeding and prolapse disappeared immediately after injection of the sclerosing agent OC-108 into submucosa of hemorrhoids. The aim of this study was to elucidate the mechanism of action responsible for the immediate hemostatic effect of OC-108 using anesthetized rats. Subcutaneous injection o...

    journal_title:Journal of pharmacological sciences

    pub_type: 杂志文章

    doi:10.1254/jphs.fp0060583

    authors: Ono T,Nakagawa H,Fukunari A,Hashimoto T,Komatsu H

    更新日期:2006-11-01 00:00:00