Leukotriene B4 is an indirectly acting vasoconstrictor in guinea pig aorta via an inducible type of BLT receptor.
Leukotriene B(4) (LTB(4)) is a potent leukocyte chemoattractant recently implicated in the pathogenesis of atherosclerosis. The aim of this study was to assess the effects of LTB(4) on isolated aortic preparations. Rings of guinea pig aorta were challenged with LTB(4) for recording mechanical responses and measurements of mediator release, and LTB(4) receptor (BLT(1)) expression was assessed by RT-PCR. Single concentrations of LTB(4) induced concentration-dependent contractions that were inhibited by treatment with antihistamines, indomethacin, or the thromboxane receptor antagonist BAYu3405 as well as by denudation of endothelium. In addition, LTB(4) increased the release of histamine and thromboxane in the bath. The contractions induced by LTB(4) were inhibited by either the unselective BLT receptor antagonist ONO-4057 or the selective BLT(1) receptor antagonist U-75302. Pretreatment with all-trans-retinoic acid enhanced the contractions and the release of histamine induced by LTB(4), without affecting either the contractions induced by histamine or the histamine release evoked by calcium ionophore A23187. Analysis by RT-PCR indicated the expression of a BLT(1) receptor in the guinea pig aorta and that BLT(1) receptor mRNA was upregulated after treatment with retinoic acid. These results suggest that LTB(4) contracts the guinea pig aorta via an indirect mechanism involving the release of histamine and thromboxane and that this BLT(1) receptor-mediated response can be upregulated by all-trans-retinoic acid.
Bäck
Magnus
M
Division of Physiology, The National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Magnus.Back@cmm.ki.se
Qiu
Hong
H
Haeggström
Jesper Z
JZ
Sakata
Kiyoto
K
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D018102:Receptors, Leukotriene B4 / Q000502:physiology*; D013931:Thromboxanes / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D018102:Receptors, Leukotriene B4; D013931:Thromboxanes; D014662:Vasoconstrictor Agents; D007975:Leukotriene B4; D014212:Tretinoin