Abstract:
:Cardiac hypertrophy causes heart failure and is associated with hyperglycemia in patients with diabetes mellitus. Mibefradil, which acts as a T-type calcium channel blocker, exerts beneficial effects in patients with heart failure. In this study, we explored the effects and mechanism of mibefradil on high-glucose-induced cardiac hypertrophy in H9c2 cells. H9c2 cells were incubated in a high-glucose medium and then treated with different concentrations of mibefradil in the presence or absence of the Akt inhibitor MK2206 or mTOR inhibitor rapamycin. Cell size was evaluated through immunofluorescence, and mRNA expression of cardiac hypertrophy markers (atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain) was assessed by using quantitative real-time polymerase chain reaction. Changes in the expression of p-PI3K, p-Akt, and p-mTOR were evaluated using Western blotting, and autophagosome formation was detected using transmission electron microscopy. Our results indicate that mibefradil reduced the size of H9c2 cells, decreased mRNA expression of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain, and decreased the level of autophagic flux. However, MK2206 and rapamycin induced autophagy and reversed the effects of mibefradil on high-glucose-induced H9c2 cells. In conclusion, mibefradil ameliorated high-glucose-induced cardiac hypertrophy by activating the PI3K/Akt/mTOR pathway and inhibiting excessive autophagy. Our study shows that mibefradil can be used therapeutically to ameliorate cardiac hypertrophy in patients with diabetes mellitus.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Zhao LG,Li PL,Dai Y,Deng JL,Shan MY,Chen B,Zhang KB,Guo SD,Xu ZHdoi
10.1097/FJC.0000000000000844subject
Has Abstractpub_date
2020-08-01 00:00:00pages
246-254issue
2eissn
0160-2446issn
1533-4023journal_volume
76pub_type
杂志文章abstract::Hypertension is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. This study was undertaken to investigate the effects of veratric acid (VA) on blood pressure, plasma, and tissue lipid profile in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Hypert...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31824f9174
更新日期:2012-06-01 00:00:00
abstract::The pulmonary vascular reactivity to endothelin-1 (ET-1) was assessed in rats previously exposed to 11% O2 (hypoxic) or room air (controls) for 3 weeks. In isolated control lung preparations studied during conditions of increased tone by U46619 (50 pmol/min) and treated with meclofenamate (3 microM), low doses of ET-1...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00102
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abstract::No single pathophysiologic mechanism explains adequately cold-induced vasospasm in all forms of Raynaud's phenomenon. Local serotonin release from activated platelets is a contributory element in those disorders typified by structural arterial change, e.g., systemic sclerosis (scleroderma). Selective antagonism of S2-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,评审
doi:
更新日期:1985-01-01 00:00:00
abstract::The relationship between arterial pressure and the rate of Na+ excretion is regulated by a number of mechanisms- some well known, some newly discovered, and probably some yet to be discovered. These mechanisms affect either the amount of Na+ filtered at the glomerulus or its rate of reabsorption from the proximal or d...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1995-01-01 00:00:00
abstract::Heart failure is unique among the major cardiovascular disorders in that it alone is increasing in prevalence while there has been a striking decrease in other conditions. Some of this can be attributed to the aging of the U.S. and European populations. The ability to salvage patients with myocardial damage is also a ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200111002-00015
更新日期:2001-11-01 00:00:00
abstract::Bromocriptine, a dopamine (DA) receptor agonist, has been reported to have hypotensive effects in anesthetized and conscious normotensive rats but its mechanism of action is still not fully understood. Therefore, we studied the changes in mean arterial blood pressure (MAP) and heart rate (HR) elicited by an intravenou...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199109000-00003
更新日期:1991-09-01 00:00:00
abstract::This selective review of a few of the advances made in recent years indicates that we are entering a new era in cardiovascular pharmacology. Drugs with novel mechanisms of action, and modifications of existing drugs, are being developed in constantly increasing numbers. The clinical evaluation of these drugs will be a...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1984-01-01 00:00:00
abstract::Previous studies have suggested the presence of nitric oxide synthase (NOS) enzyme in human platelets. We herein provide definitive evidence for the presence of both endothelial constitutive NOS (ecNOS) and inducible NOS (iNOS) isoforms and their mRNA in human platelets. Total RNA was isolated from human platelets, an...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199601000-00024
更新日期:1996-01-01 00:00:00
abstract::Phosphatidylinositol 4,5-bisphosphate hydrolysis at the plasma membrane by phospholipase C is one of the major hormone regulated intracellular signaling systems. The system generates the diffusible second messenger IP3 and the membrane bound messenger diacylglycerol. Spatial regulation of this system has been thought ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000195
更新日期:2015-03-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::The effects of tilisolol, a nonselective beta-adrenoceptor blocker, on transmembrane ionic currents were studied in single guinea pig ventricular myocytes by using the whole-cell voltage clamp technique. In the absence of beta-adrenergic stimulation, 10 microM tilisolol, a concentration higher than that used in the cl...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199705000-00005
更新日期:1997-05-01 00:00:00
abstract::To explore endothelium-dependent relaxation and the L-arginine (L-ARG)-nitric oxide (NO) pathway during chronic hypoxia, we examined isolated rings from large conduit pulmonary arteries and aorta from rats exposed to either room air (N), 3-week hypoxia (H), or 3-week H followed by 72-h recovery to normoxia (room air)....
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199312000-00018
更新日期:1993-12-01 00:00:00
abstract::This study attempted to characterize Ca2+ channels involved in endothelin-1-induced contraction of rabbit basilar artery using whole-cell patch-clamp and measurement of intracellular free Ca2+ concentration. Endothelin-1 activates two types of Ca2+-permeable nonselective cation channels (NSCC-1 and NSCC-2) and a store...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200209000-00013
更新日期:2002-09-01 00:00:00
abstract::In this report, alterations between the electrical and mechanical responses of isolated neonatal and adult canine ventricular muscle preparations before and after ouabain exposure are described. No significant differences were observed between the two age groups in the concentration-dependent effects of ouabain on inc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198911000-00002
更新日期:1989-11-01 00:00:00
abstract::Genetic hypertension [essential hypertension (EH) in humans and spontaneous hypertension in rats (SHRs)] is associated with an altered vascular structure, expressed in resistance vessels (small arteries) as an increased media:lumen ratio. The vascular smooth muscle cells appear normal and there is no cellular hypertro...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199219002-00006
更新日期:1992-01-01 00:00:00
abstract::The cardioprotective effects of bisoprolol were studied in a rat model of severe heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups: 0.1 mg/kg/day bisoprolol (Group 0.1), 1.0 mg/kg/day bisoprolol (Group 1) and 10 mg/kg/day bisoprolol (Group 1...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200110001-00012
更新日期:2001-10-01 00:00:00
abstract::Adenosine and verapamil have successfully been used in the treatment of clinical no-reflow after direct angioplasty for acute myocardial infarction. However, their effects on anatomic perfusion defects in experimental myocardial ischemia/reperfusion are unknown. Thus the area of no-reflow (ANR), visualized after in-vi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200404000-00014
更新日期:2004-04-01 00:00:00
abstract::The effects of streptozotocin (STZ)-induced diabetes (DM) and insulin on cardiac performance were investigated during reperfusion after low-flow ischemia in rats. Hearts were isolated 4 weeks after intravenous injection of STZ (65 mg/kg) or vehicle and retrogradely perfused in the presence (throughout the perfusion pe...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200210000-00001
更新日期:2002-10-01 00:00:00
abstract::The potential therapeutic value of a new prostacyclin analogue, (4z, 16s)-4,5,18,18,19,19-hexadehydro-16,20-dimethyl-delta 6(9a)- 9-(O)-methano-PGI1 (KP-10614), was studied in acute myocardial infarction in rats. Myocardial infarction was induced by ligation of the left coronary artery and ischemic injury was followed...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199210000-00017
更新日期:1992-10-01 00:00:00
abstract::The cardioprotective effects of betaxolol were studied in a rat model with heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups; 0.1 mg/kg betaxolol per day (group 0.1), 1.0 mg/kg betaxolol per day (group 1), 10 mg/kg betaxolol per day (group 1...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:2003-01-01 00:00:00
abstract::The complex formed between endothelin (ET) and its binding protein was adequately stable to be separated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) at low temperature. Cross-linking was not necessary. This simple method was applied for both qualitative (determination of molecular weight ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199100177-00028
更新日期:1991-01-01 00:00:00
abstract::The CARTAGOMAX study assessed the safety and efficacy of bivalirudin during real-world cardiac intervention. This was a single-center prospective study. Patients with acute coronary syndrome undergoing percutaneous coronary intervention were anticoagulated with bivalirudin alone or unfractionated heparin plus a glycop...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000411
更新日期:2016-09-01 00:00:00
abstract::Endothelin-1 (ET-1) in the central nervous system has been suggested to produce suppressive effects on pain transmission. We investigated the manner by which ET-1 exerts this action. ET-1 administered intracerebroventricularly produced a dose-dependent antinociceptive effect in a thermal pain test that utilized a spin...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166271.40044.0c
更新日期:2004-11-01 00:00:00
abstract::Using micropuncture techniques in euvolemic adult male Munich-Wistar rats, we assessed the functional role of renal beta-adrenoceptors in mediating neural control of glomerular filtration and proximal tubular reabsorption. The determinants of nephron filtration and rate of proximal tubular reabsorption were measured i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199103000-00007
更新日期:1991-03-01 00:00:00
abstract::During the healing phase of evolving myocardial infarction, inflammatory cells invade the affected region and produce metabolites that may influence electrophysiological parameters and the genesis of malignant arrhythmias. We have recently shown an increased synthetic capacity within an evolving infarct for thromboxan...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198511000-00009
更新日期:1985-11-01 00:00:00
abstract::The electrophysiologic and antiarrhythmic effects of oral and intravenous UM424 were studied in canine models of acute and chronic myocardial injury. In the first phase of this study, reentrant ventricular tachyarrhythmias and/or ventricular fibrillation were initiated by programmed electrical stimulation techniques i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198503000-00001
更新日期:1985-03-01 00:00:00
abstract::Structurally and pharmacologically diverse vasodilators are known to lower blood pressure, increase heart rate, and produce acute injury to right coronary arteries in the dog. Administration of low concentrations of endothelin-1 (ET-1) to anesthetized dogs causes coronary vasoconstriction and reductions in coronary bl...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199800001-00109
更新日期:1998-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::The vulnerable period (VP) is an interval of time during the cardiac cycle within which premature stimulation may lead to trains of responses (one: many stimulus-response coupling). Although the VP parallels the recovery of sodium channel availability, modulators of its boundaries remain unclear. Numerical studies of ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::Coronary artery disease is the most important cause of morbidity and mortality in Western countries. Its pathogenesis is unknown but involves an enhanced vasoconstriction and increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration, and extracellular matrix formation o...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1994-01-01 00:00:00