Metformin improves cardiac function in rats via activation of AMP-activated protein kinase.


:1. Metformin is one of the most commonly used drugs for the treatment of Type 2 diabetes. Accumulating evidence suggests that metformin also has cardioprotective effects. In the present study, we investigated the cardioprotective effects of metformin and the mechanisms involved. 2. A rat model of chronic heart failure was established by permanent left coronary artery occlusion. Heart failure rats were randomly divided into four groups: (i) a saline-treated group given 4 mL/kg day via intragastric gavage; (ii) a metformin-treated group, given 100 mg/kg metformin once daily via intragastric gavage; (iii) a group treated with 5 mg/kg 5'-aminoimidazole-4-carboxyamide-ribonucleoside (AICAR), an AMP-activated protein kinase (AMPK) agonist, every second day; and (iv) a group treated with 100 mg/kg per day metformin + 20 mg/kg, i.p., compound C (an AMPK antagonist). After 4 weeks treatment, echocardiography was used to assess left ventricular (LV) dimensions and function. Expression of AMPK, endothelial nitric oxide synthase (eNOS) and transforming growth factor (TGF)-β1 was determined by reverse transcription-polymerase chain reaction and western blot analysis. 3. Metformin administration significantly improved cardiac function and LV remodelling, as evidenced by increases in LV systolic pressure and LV ejection fraction and decreases in LV end-diastolic diameter and LV end-systolic diameter. These beneficial effects of metformin were associated with increased AMPK and eNOS phosphorylation, as well as reductions in insulin, TGF-β1, basic fibroblast growth factor and tumour necrosis factor-α levels in the circulation and/or myocardium. 4. The results indicate that chronic low-dose metformin confers significant cardioprotective effects against chronic heart failure by activating the AMPK-eNOS pathway.


Wang XF,Zhang JY,Li L,Zhao XY,Tao HL,Zhang L




Has Abstract


2011-02-01 00:00:00












  • In Vitro electrophysiological activity of nerispirdine, a novel 4-aminopyridine derivative.

    abstract::Summary 1. The non-selective K(+) channel blocker 4-aminopyridine (4-AP) has shown clinical efficacy in the treatment of neurological disorders such as multiple sclerosis. The clinical usefulness of 4-AP is hampered by its ability to produce seizures. Nerispirdine, an analogue of 4-AP, is currently under clinical inve...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Smith C,Kongsamut S,Wang H,Ji J,Kang J,Rampe D

    更新日期:2009-11-01 00:00:00

  • Dihydrocyclosporin D in sheep: haemodynamic and renal effects.

    abstract::1. This study was designed to test the haemodynamic and renal effects in sheep of dihydrocyclosporin D (dCyD), an immunosuppressant agent derived from the fungus Tolypocladium inflatum Gams. 2. dCyD was infused for 5 days at 12 mg/kg per day. Mean arterial pressure (MAP) was elevated after 24 h, but thereafter returne...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Tresham JJ,Whitworth JA,de Lima JJ,McDougall JG,Scoggins BA

    更新日期:1988-05-01 00:00:00

  • Mineralocorticoids are not involved in the antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat.

    abstract::1. In order to determine whether the antihypertensive effect of neonatal thymectomy in genetically hypertensive rats could be mediated through altered adrenal function, systolic blood pressure (SBP) and urinary excretion of deoxycorticosterone (DOC), corticosterone (B) and aldosterone were measured in thymectomized hy...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Bataillard A,Gomez-Sanchez CE,Vincent M,Touraine JL,Sassard J

    更新日期:1988-11-01 00:00:00

  • Chaotic characteristics of renal nerve peak interval sequence in normotensive and hypertensive rats.

    abstract::1. The use of non-linear dynamic analysis for the measurement of control processes in low-dimensional signals, for example, blood pressure and heart rate variability, are well established and accepted. However, the application of these analytical techniques to a high-dimensional signal, such as renal sympathetic nerve...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Zhang T,Johns EJ

    更新日期:1998-11-01 00:00:00

  • Enhancement by endothelin-1 of the release of catecholamines from the canine adrenal gland in response to splanchnic nerve stimulation.

    abstract::1. The effect of endothelin-1 on the release of adrenal catecholamines was examined in anaesthetized dogs. 2. Splanchnic nerve stimulation (SNS) at 1 and 3 Hz was applied before and after the intravenous injection of endothelin-1. 3. Endothelin-1 (0.1 and 0.3 micrograms/kg) significantly enhanced the release of adrena...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Takeuchi A,Kimura T,Satoh S

    更新日期:1992-09-01 00:00:00

  • Controlled study of the effects of dietary protein on blood pressure in normotensive humans.

    abstract::1. The object of this study was to determine whether meat protein per se is responsible for the higher blood pressures (BP) in omnivores compared with vegetarians. 2. Assessments were made by a double blind randomized control trial in 64 normotensive volunteers recruited from Royal Perth Hospital staff. 3. All volunte...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Prescott SL,Jenner DA,Beilin LJ,Margetts BM,Vandongen R

    更新日期:1987-03-01 00:00:00

  • Effect of ethamsylate on carrageenan-induced rat paw oedema: a comparison with indomethacin.

    abstract::1. Ethamsylate (diethylammonium 2,5-dihydroxybenzene sulfonate, Dicynene), a systemic haemostatic agent with an unknown mechanism of action, was tested for anti-inflammatory activity using the carrageenan-induced rat paw oedema test. 2. Ethamsylate was shown to be an effective anti-inflammatory agent with a time cours...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Gard PR,Trigger DJ

    更新日期:1990-12-01 00:00:00

  • A rat model of ischaemic or dilated cardiomyopathy for investigating left ventricular repair surgery.

    abstract::1. The effects of left ventricular repair (LVR) surgery for ischaemic or dilated cardiomyopathy are not fully understood. The development of a proper animal model will help to resolve this issue. 2. The ischaemic cardiomyopathy (ICM) model used was as follows. Twenty-six rats developed ICM with a large akinetic left v...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Nishina T,Miwa S,Yuasa S,Nishimura K,Komeda M

    更新日期:2002-08-01 00:00:00

  • Dissociation of blood pressure and sympathetic activation of renin release in sinoaortic-denervated rats.

    abstract::1. Blood pressure (BP) and heart rate (HR) increase 6 and 24 h after sinoaortic baroreceptor denervation (SAD), whereas plasma renin activity (PRA) and renal renin mRNA levels remain unchanged. We postulated that a simultaneous rise in BP could offset the expected activation of renin associated with an increased renal...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Krieger MH,Moreira ED,Oliveira EM,Oliveira VL,Krieger EM,Krieger JE

    更新日期:2006-05-01 00:00:00

  • Lack of inotropic effect of nitric oxide on the rat myocardium.

    abstract::1. Nitric oxide (NO) is an important mediator of contractile function in the heart. However, isolated papillary muscle preparations appear to lack NO responsiveness in certain animal species. Although cat, guinea-pig and ferret models have been NO responsive, there have been mixed results in the rat papillary muscle. ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Worthley MI,Horowitz JD,Zeitz CJ

    更新日期:2005-07-01 00:00:00

  • Heat-killed Salmonella typhimurium mitigated radiation-induced lung injury.

    abstract::Radiation-induced lung injury (RILI) is a serious complication in thoracic tumour radiotherapy. It often occurs in clinical chest radiotherapy and acute whole-body irradiation (WBI) caused by nuclear accidents or nuclear weapon attack. Some radioprotective agents have been reported to exert protective effects when giv...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Kun C,Tao L,Leiyuan H,Yunhao F,Ning W,Zhe L,Yuanyuan C,Xiao L,Hongran Q,Jianming C,Fu G,Yanyong Y

    更新日期:2019-12-01 00:00:00

  • Resveratrol induces gastric cancer cell apoptosis via reactive oxygen species, but independent of sirtuin1.

    abstract::The currently available chemotherapeutic regimens against gastric cancer are not very effective, leading to high recurrence and poor survival. Resveratrol is a naturally occurring polyphenol with potent apoptosis-inducing activity. However, the mechanism underlying its actions remains unknown. In the present study, hu...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Wang Z,Li W,Meng X,Jia B

    更新日期:2012-03-01 00:00:00

  • Effect of furazolidone and nitrofurazone on brain gamma-amino butyric acid and glutamate concentrations in chickens.

    abstract::1. The concentrations of gamma-amino butyric acid (GABA) and glutamate were measured in the brains of chickens which were treated with furazolidone (FZ) or nitrofurazone (NF) at oral doses of 12.5, 25 or 50 mg/kg for 5 days. 2. At the end of the treatment, birds on the small dose of FZ or NF lost about 9% of their bod...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Ali BH

    更新日期:1988-12-01 00:00:00

  • Renin gene expression in various tissues determined by single-step polymerase chain reaction.

    abstract::1. Renin mRNA is present in the kidney and, in lower concentrations, in many extrarenal tissues and serves as an index of renin gene activity, as well as potential renin or prorenin synthesis in cell populations within those tissues. Unfortunately the quantity can be very low. 2. A new, highly sensitive technique is d...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Lou YK,Smith DL,Robinson BG,Morris BJ

    更新日期:1991-05-01 00:00:00

  • Transient receptor potential (TRP) channels, vascular tone and autoregulation of cerebral blood flow.

    abstract::Members of the transient receptor potential (TRP) channel superfamily are present in vascular smooth muscle cells and play important roles in the regulation of vascular contractility. The TRPC3 and TRPC6 channels are activated by stimulation of several excitatory receptors in vascular smooth muscle cells. Activation o...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Brayden JE,Earley S,Nelson MT,Reading S

    更新日期:2008-09-01 00:00:00

  • Effect of ATP on Ca2+ uptake in the presence of high glucose in renal proximal tubule cells.

    abstract::1. Calcium regulation has been reported to be associated with the development of diabetic nephropathy. Thus, changes in Ca2+ uptake induced by ATP, an important regulator of Ca2+ uptake, in the diabetic condition and related signal pathways were examined in primary cultures of rabbit renal proximal tubule cells (PTC)....

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Han HJ,Park SH,Lee YJ,Lee JC,Lee JH

    更新日期:2003-09-01 00:00:00

  • Naloxone blocks the cardiac effects of myocardial ischaemia and reperfusion in the rat isolated heart.

    abstract::The effects of naloxone on contractility and cardiac rhythm were studied in the rat isolated perfused heart during myocardial ischaemia and reperfusion. Pretreatment of the rat isolated perfused heart with naloxone abolished the reduction in left ventricular pressures and attenuated greatly the arrhythmias due to myoc...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Zhan ZY,Lee AY,Wong TM

    更新日期:1985-07-01 00:00:00

  • Recombinant human hepatocyte growth factor (HGF), but not rat HGF, elicits glomerular injury and albuminuria in normal rats via an immune complex-dependent mechanism.

    abstract::1. Hepatocyte growth factor (HGF) has the therapeutic potential to improve renal fibrosis and proteinuria in rodents with chronic kidney disease. In contrast, long-term administration of human HGF to normal rats reportedly elicits proteinuria. Thus, the role of HGF during proteinuria remains contentious. The aim of th...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Mizuno S,Ikebuchi F,Fukuta K,Kato T,Matsumoto K,Adachi K,Abe T,Nakamura T

    更新日期:2011-03-01 00:00:00

  • Comparison of neurite outgrowth with neurofilament protein subunit levels in neuroblastoma cells following mercuric oxide exposure.

    abstract::1. The objectives of the study were to establish that inhibition of neuronal differentiation in culture (assessed by neurite outgrowth) can be used as a broad spectrum in vitro measure of neurotoxicity. 2. To establish whether a rapid measure of neurite outgrowth could be used. Thus the study examined the relationship...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Abdulla EM,Calaminici M,Campbell IC

    更新日期:1995-05-01 00:00:00

  • Increased cardiac sympathetic drive and reduced vagal modulation following endothelin receptor antagonism in healthy conscious rats.

    abstract::1. The present study evaluated changes in autonomic control of the cardiovascular system in conscious rats following blockade of endothelin (ET) receptors with bosentan. 2. Rats were treated with bosentan or vehicle (5% gum arabic) for 7 days by gavage. 3. Baseline heart rate (HR) was higher in the bosentan-treated gr...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Souza HC,Terzini GC,da Silva VJ,Martins-Pinge MC,Salgado HC,Salgado MC

    更新日期:2008-07-01 00:00:00

  • Actions of the anti-oestrogen agent clomiphene on outward K+ currents in rat ventricular myocytes.

    abstract::1. The effects of clomiphene (CLM) on cardiac outward K+ current components from rat isolated ventricular myocytes were investigated using the whole-cell patch-clamp technique. Clomiphene (10 micromol/L) significantly inhibited both peak (Ipeak) and end-pulse (Ilate) outward currents (elicited by a 500 msec voltage st...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Borg JJ,Hancox JC,Hogg DS,James AF,Kozlowski RZ

    更新日期:2004-01-01 00:00:00

  • From 'captive' agonism to insurmountable antagonism: demonstrating the power of analytical pharmacology.

    abstract::1. Mathematical modelling is useful in pharmacology, allowing the investigator to obtain insights into the biological processes under study that may not always be intuitively obvious. Examples are presented in this review using the pharmacology of the muscarinic acetylcholine receptor (mAChR) agonist xanomeline. 2. Xa...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章,评审


    authors: Christopoulos A

    更新日期:2001-03-01 00:00:00

  • Intracerebroventricular ANP(1-28) has no obvious effects on renal blood flow and function in conscious sheep.

    abstract::1. The study examines whether intracerebroventricular (ICV) infusion of atrial natriuretic peptide (human ANP,1-28) influences renal electrolyte and water excretion, vasopressin release, renal and femoral blood flows in conscious ewes. The blood flow was measured by chronically implanted ultrasonic flow probes. 2. ICV...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Gunnarsson U

    更新日期:1994-03-01 00:00:00

  • HERG-F463L potassium channels linked to long QT syndrome reduce I(Kr) current by a trafficking-deficient mechanism.

    abstract::1. Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease. The aim of the present study was to identify the gene mutation in a Chinese family with LQTS and investigate the functional changes associated with the mutation. 2. Polymerase chain reaction and DNA sequencing were used to screen for the KCN...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Yang HT,Sun CF,Cui CC,Xue XL,Zhang AF,Li HB,Wang DQ,Shu J

    更新日期:2009-08-01 00:00:00

  • Role of non-selective adenosine receptor blockade and phosphodiesterase inhibition in cisplatin-induced nephrogonadal toxicity in rats.

    abstract::1. It is well documented that cisplatin (CDDP) treatment increases the expression of adenosine A(1) receptors in both kidney and testes. However, the effect of adenosine at these receptors is controversial. Adenosine A(1) receptors have been documented to be involved in either cytoprotection or aggravation of nephroto...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Saad SY,Najjar TA,Alashari M

    更新日期:2004-12-01 00:00:00

  • Structure of human renin and expression of the renin gene.

    abstract::The amino acid sequence of human renin was identified for the first time. This was determined from the nucleotide sequence of exons in the human renin gene identified in a genomic library by recombinant DNA techniques. Examination of amino acid residues involved in the enzymatic hydrolysis by human renin of the unique...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Morris BJ,Catanzaro DF,Hardman J,Mesterovic N,Tellam J,Hort Y,Bennetts BH,Shine J

    更新日期:1984-07-01 00:00:00

  • Cellular calcium regulatory machinery of vasorelaxation elicited by petasin.

    abstract::1. The present study examined the cytosolic Ca(2+) regulatory machinery involved in the vasorelaxation produced by petasin, a sesquiterpene isolated from Petasites formosanus. 2. Aortic rings isolated from Sprague-Dawley rats were exposed to petasin (0.01-100 micromol/L) to elucidate its vascular effects on isometric ...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Wang GJ,Lin YL,Chen CH,Wu XC,Liao JF,Ren J

    更新日期:2010-03-01 00:00:00

  • Vasopressin V1a receptor antagonism does not reverse adrenocorticotrophin-induced hypertension in the rat.

    abstract::1. The role of arginine vasopressin (AVP) was examined in adrenocorticotrophin (ACTH)-induced hypertension in Sprague-Dawley rats using the non-peptide AVP V1a receptor antagonist OPC 21268. 2. In an acute study, six rats were pretreated with ACTH for 11 days and direct arterial blood pressure (4 h), plasma osmolality...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: Fraser TB,Turner SW,Wen C,Li M,Burrell LM,Whitworth JA

    更新日期:2000-11-01 00:00:00

  • Fixed dose of long-acting erythropoietic stimulating agents at higher frequency improves appetite, reduces inflammation and corrects anaemia in patients on haemodialysis.

    abstract::Anaemia is an important issue in patients undergoing haemodialysis. We aimed to identify a better dosing schedule of a fixed monthly dose of continuous erythropoietin receptor activator (CERA) in patients with chronic kidney disease (CKD) on haemodialysis. The CERA dosing schedule included 100 μg once monthly for 2 mo...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Liu WS,Chu DC,Chan HL,Li SY,Liu CK,Yang CY,Chen YW,Lee PC,Lai YT,Lin CC

    更新日期:2016-10-01 00:00:00

  • Inhibition of cardiac baroreflex sensitivity after central dopaminergic stimulation.

    abstract::1. Stimulation of the mesolimbic dopamine system, by micro-injection of the substance P analogue [pGlu5,MePhe8,Sar9] substance P (DiMe-C7) into the ventral tegmental area induced a prolonged increase in blood pressure and circulating levels of vasopressin. 2. In the present study, this treatment produced a significant...

    journal_title:Clinical and experimental pharmacology & physiology

    pub_type: 杂志文章


    authors: van den Buuse M,Wilks DP,Cornish JL

    更新日期:1998-07-01 00:00:00