title: Cysteinyl leukotrienes and leukotriene B mediate vasoconstriction to arginine vasopressin in rat basilar artery.
abstract: 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. 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. Leukotriene D4, LTC4 and LTB4 acted as vasoconstrictor agents in rat basilar artery, causing contractions (all at concentrations of 1 micromol/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 determined. The presence of the 5-lipoxygenase inhibitors ZM 230487 (10 nmol/L and 0.1 and 1 micromol/L) and AA 861 (1, 3, 10, and 30 micromol/L), the CysLT1 receptor antagonist MK 571 (3, 10 and 30 micromol/L) or the BLT receptor antagonists CP 105696 and LY 255283 (3, 10 and 30 micromol/L for both) in the organ bath significantly attenuated the contractions induced by AVP in rat basilar artery (P < 0.05). 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.
authors.affiliation: Pharmacology Division, Radioisotope Research Center, Kyoto University, Kyoto, Japan.
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Trandafir
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nishihashi
authors.forename: Xu
authors.initials: X
authors.lastname: Ji
authors.forename: Aimin
authors.initials: A
authors.lastname: Wang
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Kurahashi
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001488:Basilar Artery / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D020024:Leukotriene Antagonists / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000494:pharmacology*; D017998:Leukotriene D4 / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018077:Receptors, Leukotriene / Q000187:drug effects; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D002264:Carboxylic Acids; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors; D011422:Propionates; D011804:Quinolines; D018077:Receptors, Leukotriene; D018102:Receptors, Leukotriene B4; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D007975:Leukotriene B4; D017997:Leukotriene C4; C059141:verlukast; D017998:Leukotriene D4; C063823:LY 255283; C089698:CP 105696