Cysteinyl leukotrienes and leukotriene B4 mediate vasoconstriction to arginine vasopressin in rat basilar artery

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) B-4, 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 CysLT(1) or BLT receptor antagonists. Contractile responses to leukotrienes and ANIP are expressed as a percentage of the contraction induced by 80 mmol/L KCl. 3. Leukotriene D-4, LTC4 and LTB4 acted as vasoconstrictor agents in rat basilar artery, causing contractions (all at concentrations of 1 mu mol/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 mu mol/L) and AA 861 (1, 3, 10, and 30 mu mol/L), the CysLT(1) receptor antagonist MK 571 (3, 10 and 30 mu mol/L) or the BLT receptor antagonists CP 105696 and LY 255283 (3, 10 and 30 mu mol/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.