Abstract：
:We have demonstrated that activation of ATP-sensitive potassium (K(ATP)) channels can attenuate sympathetic hyperinnervation. Sildenafil, a phosphodiesterase-5 inhibitor, has been shown to provide a preconditioning-like cardioprotective effect via opening of K(ATP) channels. The aim of this study was to investigate whether chronic administration of sildenafil attenuates cardiac sympathetic hyperinnervation after myocardial infarction through activation of K(ATP) channels and to compare it with the nitric oxide donor isosorbide dinitrate. Male Wistar infarcted rats induced by ligation of the anterior descending artery were randomized to either vehicle, nicorandil, sildenafil, isosorbide dinitrate, glibenclamide, or a combination of nicorandil and glibenclamide, or sildenafil and glibenclamide. Myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats compared with sham-operated rats, consistent with sympathetic hyperinnervation after infarction assessed by immunohistochemical analysis for tyrosine hydroxylase, growth associated factor 43 and neurofilament and by protein expression and mRNA of nerve growth factor. Sympathetic hyperinnervation was reduced after administering either nicorandil or sildenafil. Arrhythmic scores during programmed stimulation in the sildenafil-treated rats were significantly lower than those treated with the vehicle. Furthermore, the beneficial effects of sildenafil-induced were reversed by the addition of either glibenclamide or 5-hydroxydecanoate, implicating mitochondrial K(ATP) channels as the relevant target. Isosorbide dinitrate failed to confer similar antiarrhythmia. 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one, a soluble guanylyl cyclase inhibitor, did not influence the effect of sildenafil on the nerve growth factor. These data indicate that sildenafil after infarction attenuated sympathetic hyperinnervation and arrhythmias by activation of mitochondrial K(ATP) channels through a guanylyl cyclase-cGMP-independent pathway.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Lee TM,Chen CC,Chung TH,Chang NCdoi
10.1016/j.ejphar.2012.05.015subject
Has Abstractpub_date
2012-09-05 00:00:00pages
124-32issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(12)00442-6journal_volume
690pub_type
杂志文章abstract：:Transfected Chinese hamster ovary cells expressing human alpha2A-, alpha2B- and alpha2C-adrenoceptor subtypes were used to monitor alpha2-adrenoceptor-stimulated GTP hydrolysis. Incubation with 100 microM (-)-adrenaline resulted in stimulation of pertussis toxin-sensitive GTPase by 380% after activation of the alpha2A...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00306-4
更新日期：1999-06-11 00:00:00
abstract：:The interaction of the delta-opiate agonist [D-Ala2,D]Leu5]enkephalin (DADL) with the mu-opiate ligands dihydromorphine (DHM) and naloxone and the kappa-opiate ligand ethylketocyclazocine (EK) was studied in rat diencephalic membranes which contain mainly mu-opiate binding sites. Saturation binding experiments perform...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90145-5
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abstract：:The relationship between isometric tension and the increase in cyclic GMP level associated with the initial phase of drug-induced contraction of taenia coli was studied. Maximal contraction induced by 100 micrometers carbachol or 124 mM KCl occurred in 30 sec and was associated with an increase in cyclic GMP levels of...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90209-0
更新日期：1981-03-12 00:00:00
abstract：:Intravenous (i.v.) administration of cytidine-5'-diphosphate choline (CDP-choline) (100, 250 and 500 mg/kg) increased blood pressure in normal rats and reversed hypotension in haemorrhagic shock. Choline (54 mg/kg; i.v.), at the dose equimolar to 250 mg/kg CDP-choline decreased blood pressure of rats in both condition...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01602-9
更新日期：2003-05-09 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90357-5
更新日期：1976-11-01 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90227-9
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90230-x
更新日期：1986-05-27 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90357-n
更新日期：1993-03-16 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90272-0
更新日期：1989-05-30 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
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更新日期：2014-01-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.02.001
更新日期：2012-04-15 00:00:00
abstract：:Bimoclomol is a new compound that improves cell survival under experimental stress conditions partly by increasing intracellular heat shock proteins (HSPs). HSPs, especially HSP70, play a cytoprotective role in the rat heart. Rat neonatal cardiomyocytes were used to determine the ability of bimoclomol to induce HSP70 ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01551-5
更新日期：2002-01-18 00:00:00
abstract：:This study assessed the effects of intracerebroventricular administration of selective agonists and antagonists for tachykinin NK1 and NK2 receptors on performance of mice in the elevated plus-maze, an ethological model of anxiety. Mice were treated with either vehicle (5 microliters) or 1, 10, 100 or 500 pmol of subs...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00390-1
更新日期：1996-09-05 00:00:00
abstract：:The extracellular loops of the adrenoceptors present a potential therapeutic target in the design of highly selective adrenergic drugs. These regions are less conserved than the orthosteric binding site but have to date not been implicated in activation of adrenoceptors. A previously generated homology model identifie...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.03.034
更新日期：2014-06-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01290-0
更新日期：2001-09-28 00:00:00
abstract：:Apoptosis has received widespread attention for its essential roles in biology, medicine and cancer. We previously found that normal, human papillomavirus (HPV) 16-immortalized and their transformed endocervical cells were increasingly resistant to apoptosis induced by a cancer therapeutic drug. Here, analogously, ano...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(03)01561-9
更新日期：2003-04-25 00:00:00
abstract：:The vascular effects of bradykinin were studied in rat perfused mesenteric vascular beds with active tone. Bolus injections of bradykinin (1-1000 pmol) but not des-Arg(9)-bradykinin (bradykinin B(1) receptor agonist) induced triphasic vascular responses: the initial sharp vasodilation followed by transient vasoconstri...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01513-8
更新日期：2001-12-14 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)90412-y
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1988-04-13 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.05.047
更新日期：2013-08-15 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.04.052
更新日期：2006-08-07 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90226-7
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abstract：:The mechanisms underlying the capsaicin-induced relaxation of the acetylcholine- as well as KCl-contraction were studied by measuring isometric force and phosphorylation of 20-kDa regulatory light chain subunit of myosin (MLC(20)) in ileal longitudinal smooth muscles of rats. Capsaicin relaxed acetylcholine- and KCl-s...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.01.014
更新日期：2004-03-08 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:St. John's wort (Hypericum perforatum L.) is widely used for the treatment of mild to moderately severe depression. However, the nature of its active principles and the exact mode of antidepressant action are still unknown. It has been suggested repeatedly in preclinical and clinical studies that the content of the ac...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02818-2
更新日期：2003-01-05 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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abstract：:The effect of morphine on the capsaicin-induced cough reflex was studied in mu 1-opioid receptor-deficient CXBK mice. There was no significant difference between the morphine-induced antitussive effect in CXBK mice and C57BL/6 mice, a progenitor strain. Furthermore, the antitussive effects of morphine in both the CXBK...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90553-t
更新日期：1993-08-10 00:00:00
abstract：:Primary cultures of rat cerebellar granule neurons express 5-lipoxygenase, an enzyme from the inflammatory pathway of arachidonic acid. Outside the central nervous system (CNS) 5-lipoxygenase participates in cell proliferation. We hypothesized that 5-lipoxygenase is needed for proliferation of immature cerebellar gran...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)00924-4
更新日期：2001-04-20 00:00:00
