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  • 2005-2009  (2)
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  • 1
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Noradrenaline (NA; 0.3 µmol/L) caused a contraction of the rat coronary artery that markedly increased in the presence of the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 100 µmol/L) and arachidonic acid (1 µmol/L; P 〈 0.05).2. The present experiments attempted to elucidate the endothelium dependency of the contraction and to pharmacologically characterize the factors involved in the contraction induced by NA (0.3 µmol/L) in the presence of l-NAME and arachidonic acid in ring preparations of the rat coronary artery.3. The NA (0.3 µmol/L)-induced contraction was attenuated by a chemical remover of the endothelium (saponin at concentrations of 0.1 and 0.4 mg/mL) in a concentration-dependent manner (P 〈 0.05).4. The cyclo-oxygenase (COX)-1 inhibitor flurbiprofen (0.01–1 µmol/L) and the COX-2 inhibitor nimesulide (0.01–1 µmol/L) attenuated the NA-induced contraction in a concentration-dependent manner and the inhibitory effect of flurbiprofen was significantly more potent than that of nimesulide (P 〈 0.05). The 5-lipoxigenase inhibitor ZM-230487 (1 µmol/L) did not affect the NA-induced contraction.5. The thromboxane A2 (TXA2) synthetase inhibitor OKY-046 (30 µmol/L) and the TXA2 antagonist S-1452 (0.1–10 µmol/L) did not attenuate the NA-induced contraction.6. These results indicate that the contraction induced by NA in the rat coronary artery in the presence of l-NAME and arachidonic acid is endothelium dependent and is due to endothelial COX metabolites of arachidonic acid.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Pty
    Clinical and experimental pharmacology and physiology 32 (2005), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Arginine vasopressin (AVP) has been reported to be involved in the development of cerebral vasospasm after haemorrhage and cerebral oedema following ischaemia. Endogenously produced 5-lipoxygenase metabolites are able to contract isolated endothelium-preserved arterial strips and modulate vascular permeability. The present study addresses the role of 5-lipoxygenase and its products, namely cysteinyl leukotrienes (CysLTs) and leukotriene (LT) B4, in the contraction induced by AVP in rat basilar artery.2. Contractile responses to LTD4, LTC4, LTB4 or AVP were assessed in spiral preparations of rat endothelium-intact basilar artery. Contractions to AVP were determined in the absence or presence of 5-lipoxygenase inhibitors or CysLT1 or BLT receptor antagonists. Contractile responses to leukotrienes and AVP are expressed as a percentage of the contraction induced by 80 mmol/L KCl.3. Leukotriene D4, LTC4 and LTB4 acted as vasoconstrictor agents in rat basilar artery, causing contractions (all at concentrations of 1 µmol/L) of 42 ± 13, 54 ± 15 and 25 ± 6% of the response to 80 mmol/L KCl, respectively. A concentration–response curve was constructed for AVP over the range 1 pmol/L to 10 nmol/L and an EC50 value of 0.19 ± 0.02 nmol/L (n = 30) was determinted. The presence of the 5-lipoxygenase inhibitors ZM 230487 (10 nmol/L and 0.1 and 1 µmol/L) and AA 861 (1, 3, 10, and 30 µmol/L), the CysLT1 receptor antagonist MK 571 (3, 10 and 30 µmol/L) or the BLT receptor antagonists CP 105696 and LY 255283 (3, 10 and 30 µmol/L for both) in the organ bath significantly attenuated the contractions induced by AVP in rat basilar artery (P 〈 0.05).4. The experimental results of the present study provide the first evidence for the involvement of CysLTs and LTB4 in the in vitro constriction induced by AVP in rat basilar artery. In the context of previously reported involvement of AVP in the development of cerebral vasospasm and oedema, the present study draws attention to the potential role played by the 5-lipoxygenase pathway in these pathological processes.
    Type of Medium: Electronic Resource
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