Abstract:
BACKGROUND AND PURPOSE:8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), formed nitric oxide (NO)-dependently, is a physiological second messenger, yet little is known about its role in the pathophysiology of vascular diseases. To study the pharmacological activity of 8-nitro-cGMP in diabetic mice, we compared its effects on vascular reactivity of aortas from non-diabetic and diabetic mice. EXPERIMENTAL APPROACH:Vascular tension recording was performed in thoracic aortic rings from wild-type (C57BL/6), non-diabetic db/+ and obese/diabetic db/db mice. Endothelial NO synthase (eNOS) uncoupling and superoxide were tested by Western blot and dihydroethidium fluorescence respectively. KEY RESULTS:8-Nitro-cGMP, at concentrations up to 10 µM, enhanced phenylephrine-induced contractions in aortas from C57BL/6 and db/+ mice, but not from db/db mice. This enhancement was not observed with 8-bromo-cGMP. Pretreatment of aortas from C57BL/6 and db/+ mice with l-NAME (100 µM), superoxide dismutase (100 U·mL(-1) ) or tiron (1 mM), abolished 8-nitro-cGMP-induced enhancement of the phenylephrine contraction. In 8-nitro-cGMP (10 µM)-treated C57BL/6 aortas, eNOS dimer/monomer ratio was significantly decreased and vascular superoxide production increased, suggesting that 8-nitro-cGMP-induced superoxide production via eNOS uncoupling may mediate the enhancement of the phenylephrine contraction. At higher concentrations (>10 µM), 8-nitro-cGMP produced relaxation of the phenylephrine-contracted aortas from C57BL/6, db/+ and db/db mice. The 8-nitro-cGMP-induced relaxation in db/db mouse aortas was found to be resistant to a phosphodiesterase 5 inhibitor, zaprinast (1 µM). CONCLUSIONS AND IMPLICATIONS:The vasodilator effect of 8-nitro-cGMP may contribute to amelioration of the vascular endothelial dysfunction in diabetic mice, representing a novel pharmacological approach to prevent the complications associated with diabetes.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Tokutomi Y,Kataoka K,Yamamoto E,Nakamura T,Fukuda M,Nako H,Toyama K,Dong YF,Ahmed KA,Sawa T,Akaike T,Kim-Mitsuyama Sdoi
10.1111/j.1476-5381.2011.01201.xsubject
Has Abstractpub_date
2011-04-01 00:00:00pages
1884-93issue
8eissn
0007-1188issn
1476-5381journal_volume
162pub_type
杂志文章abstract::1 delta'-trans-Tetrahydrocannabinol (THC) is more active orally in mice than previously thought, as cataleptic responses occur at doses from 0.06 mg/kg upwards, with peak activity at 2 to 4 h after dosing. These doses and peaks correspond well with the effects in man. 2 Comparison with chlorpromazine in mice shows tha...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1979.tb08691.x
更新日期:1979-11-01 00:00:00
abstract::1 Twenty-two compounds classified as antidepressants, metabolites of antidepressants or putative antidepressants were assayed for their ability to antagonize the binding of (-)-[3H]-quinuclidinyl benzilate to muscarinic receptors in homogenates of human caudate nucleus. 2 Sixteen of these compounds were assayed for th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:UNLABELLED:Sensory neurons play important roles in many disorders, including inflammatory diseases, such as sepsis. Sepsis is a potentially lethal systemic inflammatory reaction to a local bacterial infection, affecting thousands of patients annually. Although associated with a high mortality rate, sepsis outcome depen...
journal_title:British journal of pharmacology
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doi:10.1111/bph.12056
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abstract::The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n-3), the omega-3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1 - 100 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 micro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703754
更新日期:2000-12-01 00:00:00
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journal_title:British journal of pharmacology
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doi:10.1038/sj.bjp.0707138
更新日期:2007-03-01 00:00:00
abstract::1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb06985.x
更新日期:1977-01-01 00:00:00
abstract::1. The effect of the calcitonin gene-related peptide antagonist (CGRP8-37, 400 nmol kg-1, i.v.) on the increased blood flow induced by calcitonin gene related peptide (CGRP), vasodilator prostaglandins, and topical capsaicin was measured with a laser Doppler blood flow meter in rat abdominal skin. 2. The saphenous ner...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13878.x
更新日期:1993-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/bph.14694
更新日期:2019-08-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15353.x
更新日期:1996-04-01 00:00:00
abstract::1 We have investigated the effects of loperamide on intracellular Ca(2+) stores and membrane K(+) channels in insulin-secreting hamster insulinoma (HIT-T15) cells. 2 In cell-attached patch-clamp mode, loperamide (3-250 micro M) activated large single-channel currents. The loperamide-activated currents were tentatively...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705263
更新日期:2003-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0701610
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A neg...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01795.x
更新日期:2012-05-01 00:00:00
abstract::1. Rat cultured aortic vascular smooth muscle cells (VSMC) express both cyclic GMP-inhibited cyclic AMP phosphodiesterase (PDE3) and Ro 20-1724-inhibited cyclic AMP phosphodiesterase (PDE4) activities. By utilizing either cilostamide, a PDE3-selective inhibitor, or Ro 20-1724, a PDE4-selective inhibitor, PDE3 and PDE4...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701376
更新日期:1997-09-01 00:00:00
abstract::1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 rece...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705929
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:As a hallmark of glioblastoma multiforme (GBM), CD44 plays a crucial role in promoting glioblastoma stem cell (GSC) stemness phenotypes and multiple drug resistance. The therapeutic potential of CD44 has been validated by the clinical successes of several CD44 inhibitors, including antibodies and...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15030
更新日期:2020-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb06949.x
更新日期:1975-11-01 00:00:00
abstract::Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA)...
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pub_type: 杂志文章
doi:10.1038/sj.bjp.0705641
更新日期:2004-02-01 00:00:00
abstract::1 Eleven analogues of sodium cromoglycate have been tested for their ability to suppress histamine release induced by anti-IgE from passively sensitized human lung fragments in vitro. 2 With the exception of WY 16922, which released histamine at high concentrations, all inhibited histamine release in a linear dose-rel...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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abstract::The distribution of beta-adrenoceptor subtypes in slide-mounted sections of guinea-pig kidney has been examined by the technique of in vitro labelling combined with autoradiography. Binding of (-)-[125I]-cyanopindolol (Cyp) to kidney sections equilibrated and dissociated slowly, was saturable and stereoselective with ...
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1985.tb08867.x
更新日期:1985-06-01 00:00:00
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doi:10.1038/sj.bjp.0705551
更新日期:2003-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12556.x
更新日期:1989-08-01 00:00:00
abstract::1. In guinea-pigs previously sensitized with ovalbumin, the intra-plantar administration of the antigen induced dose-dependent and sustained oedema. An intense infiltrate of neutrophils and eosinophils was observed at the peak of the oedema (4 h). 2. Oedema induced by ovalbumin at the doses of 50 or 200 micrograms/paw...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13038.x
更新日期:1994-05-01 00:00:00
abstract::1. We investigated whether K(+) can act as an endothelium-derived hyperpolarizing factor (EDHF) in isolated small renal arteries of Wistar-Kyoto rats. 2. Acetylcholine (0.001 - 3 microM) caused relaxations that were abolished by removal of the endothelium. However, acetylcholine-induced relaxations were not affected b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703965
更新日期:2001-04-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12480
更新日期:2014-01-01 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.13678
更新日期:2017-10-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb08012.x
更新日期:1969-07-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07363.x
更新日期:1975-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14075.x
更新日期:1990-08-01 00:00:00
abstract::1. Caffeine has been widely used as a pharmacological tool to evaluate Ca(2+) release from the sarcoplasmic reticulum in isolated smooth muscle cells. However, in nervous tissue this drug also causes neurotransmitters release, which might cause additional effects when smooth muscle strips are evaluated. To assess this...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705348
更新日期:2003-07-01 00:00:00
abstract::Translational sciences increasingly emphasize the measurement of functions in native human tissues. However, such studies must confront variations in patient age, gender, genetic background and disease. Here, these are discussed with reference to neuromuscular and neurosecretory functions of the human gastrointestinal...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1476-5381.2012.02198.x
更新日期:2013-01-01 00:00:00