Abstract：
BACKGROUND AND PURPOSE:The type-5 PDE inhibitor vardenafil reduces myocardial infarct size in situ, following ischemia/reperfusion, when applied at reperfusion in animal models. Little is known about the underlying protective signaling. Here, we test whether vardenafil is protective in rat isolated hearts and in a cell model of calcium stress. EXPERIMENTAL APPROACH:Infarct size in rat isolated hearts was measured after a 30 min regional ischemia and 120 min reperfusion. Vardenafil (1 nM-1 microM) was infused during reperfusion. HL-1 cardiomyocytes were loaded with tetramethylrhodamine ethyl ester (TMRE), a fluorescent marker of mitochondrial membrane potential (psi m). KEY RESULTS:Vardenafil at reperfusion reduced infarct size as percentage of the ischemic zone from 45.8+/-2.0% in control hearts to 26.2+/-2.7% (P<0.001) only at 10 nM, whereas higher or lower dosages failed to protect. This protective effect was blocked by co-administration of either the GC inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), or the PKG inhibitor, KT-5823. HL-1 cardiomyocytes, loaded with TMRE, were treated for 80 min with the calcium ionophore, calcimycin, to induce calcium stress. This reduced the mean cell fluorescence to 63.3 +/- 3.8% of baseline values and vardenafil protected against this fall (78.6 +/- 3.6%, P<0.01). The vardenafil-induced protection of HL-1 cells was blocked by ODQ, KT-5823 or the PKG-inhibiting peptides DT-2 and DT-3, confirming a role for GC and PKG. CONCLUSIONS AND IMPLICATIONS:These results further support the hypothesis that PDE-5 inhibitors are protective in ischemic hearts, in addition to their known clinical effects in the treatment of erectile dysfunction in men.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Maas O,Donat U,Frenzel M,Rütz T,Kroemer HK,Felix SB,Krieg Tdoi
10.1038/bjp.2008.71subject
Has Abstractpub_date
2008-05-01 00:00:00pages
25-31issue
1eissn
0007-1188issn
1476-5381pii
bjp200871journal_volume
154pub_type
杂志文章abstract：:1 We have investigated the effects of platelet-activating factor (PAF), an endogenous mediator of inflammation, on ion transport and prostaglandin synthesis in the human isolated colon. 2 Application of PAF to the serosal surface of human colonic mucosa induced a marked, concentration-dependent increase in ion transpo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701602
更新日期：1998-01-01 00:00:00
abstract：:1. The interaction between endogenous nitric oxide (NO) and factors from the rat submandibular salivary gland such as epidermal growth factor (EGF) on gastric mucosal integrity in the rat has been investigated. 2. Bolus administration of the NO synthase inhibitor, NG nitro-L-arginine methyl ester (L-NAME; 6.25-50 mg k...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13797.x
更新日期：1993-09-01 00:00:00
abstract：:Chronic heart failure (HF) is characterized by left ventricular (LV) structural remodeling, impaired function, increased circulating noradrenaline (NA) levels and impaired responsiveness of the myocardial beta-adrenoceptor (betaAR)-adenylyl cyclase (AC) system. In failing hearts, inhibition of the sodium/proton-exchan...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706714
更新日期：2006-05-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12247.x
更新日期：1991-03-01 00:00:00
abstract：:1. Our study was aimed at investigating the duration of the bronchodilator action of the antimuscarinc drug glycopyrrolate compared to tiotropium and ipratropium. In the guinea-pig isolated trachea, the time (t1/2) necessary for a contractile response to carbachol (0.3 microM) to return to 50% recovery after washout o...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706724
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09018.x
更新日期：1992-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706170
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11438.x
更新日期：1988-02-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1970.tb09927.x
更新日期：1970-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Gallium (Ga) has been shown to be effective in the treatment of disorders associated with accelerated bone loss, including cancer-related hypercalcemia and Paget's disease. These clinical applications suggest that Ga could reduce bone resorption. However, few studies have studied the effects of G...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00665.x
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11415.x
更新日期：1988-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Muscarinic toxins (MTs) are snake venom peptides named for their ability to interfere with ligand binding to muscarinic acetylcholine receptors (mAChRs). Recent data infer that these toxins may have other G-protein-coupled receptor targets than the mAChRs. The purpose of this study was to systema...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01468.x
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abstract：:1. The effects of cocaine, 6-hydroxydopamine (6-OHDA), reserpine and 17-beta-oestradiol on the sensitivity of the rat anococcygeus muscle to noradrenaline (NA), acetylcholine (ACh) and KCl were investigated.2. Cocaine (10(-5)M) increased the sensitivity of the anococcygeus to NA (100-fold) but not to ACh or KCl.3. 6-O...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb17261.x
更新日期：1973-11-01 00:00:00
abstract：:1. Inhibition of nitric oxide generation with Nw-nitro-L-arginine (nitroarginine) reduced vasodilator responses to bradykinin and acetylcholine and enhanced those to nitroprusside in the rat isolated perfused kidney, preconstricted with phenylephrine. 2. Inhibition of cyclo-oxygenase with indomethacin, decreased the v...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14513.x
更新日期：1992-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:5-HT (serotonin) regulates various physiological functions, both directly and via enteric neurons. The present study investigated the role of endogenous 5-HT and 5-HT3 receptors in the pathogenic mechanisms involved in colonic inflammation, especially in relation to substance P (SP) and the neuro...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13482
更新日期：2016-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702107
更新日期：1998-10-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12181.x
更新日期：1991-02-01 00:00:00
abstract：:1. The effector mechanism of intestinal necrosis in rat anaphylaxis was studied following several complementary approaches: (i) the use of monoclonal antibodies (mAb) belonging to different classes (IgG1, IgG2b and IgE anti-DNP), (ii) the assay of mediators, and (iii) the use of pharmacological tools. 2. Lethality and...
journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1994.tb13197.x
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journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0704260
更新日期：2001-09-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0705289
更新日期：2003-06-01 00:00:00
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journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0702332
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abstract：:1. We investigated the nitric oxide (NO) dependence of vasorelaxation in response to different calcium channel blockers (CCB), in rabbit femoral artery in vivo. 2. Anaesthetized rabbits underwent femoral artery ligation, and blood from the proximal artery was returned distal to the ligature through a constant infusion...
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更新日期：2002-06-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/sj.bjp.0702231
更新日期：1998-12-01 00:00:00
abstract：:1 A study was made of desensitization in chronically denervated and in normally innervated mouse soleus muscles. 2 Very high concentrations of acetylcholine produced small contractions of the innervated muscles; these were reduced in size when the addition was repeated 1 min after wash-out. 3 Desensitization in innerv...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07620.x
更新日期：1975-09-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14363
更新日期：2019-11-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701875
更新日期：1998-06-01 00:00:00
abstract：:1 Contractile responses produced by the alpha 1-adrenoceptor selective agonist, phenylephrine, and the alpha 2-adrenoceptor selective agonists, oxymetazoline and clonidine, have been compared to those produced by noradrenaline (non selective) in the rat aorta. 2 The relative order of potency of the agonists was noradr...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09337.x
更新日期：1982-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Small conductance calcium-activated potassium (KCa 2.x) channels have a widely accepted canonical function in regulating cellular excitability. In this study, we address a potential non-canonical function of KCa 2.x channels in breast cancer cell survival, using in vitro models. EXPERIMENTAL APP...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13357
更新日期：2016-01-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb09593.x
更新日期：1974-01-01 00:00:00
abstract：:The human distal gut is home to a rich and dense microbial community with representatives of all three domains of life which are intricately connected with our physiology and health. The combined genomes of these microbes, collectively called the human microbiome, vastly expand the metabolic capacities of our own geno...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14085
更新日期：2018-12-01 00:00:00
