title: Influence of endothelin on human platelet aggregation and prostacyclin generation from human vascular endothelial cells in culture.
abstract: The effects of endothelin (ET) on the function of cultured human umbilical vein endothelial cells (HUVEC) and that of human platelets were investigated with reference to endothelium-derived relaxing factor (EDRF) and PGI2. Considering the platelets, ET had no effect on platelet-rich plasma (PRP) aggregation, the generation of thromboxane A2 ([TXA2]) from platelets, and cytosolic free calcium ion concentration ([Ca++]i), cAMP content ([cAMP]i) or cGMP content ([cGMP]i) in platelets. In contrast, the addition of the solution in which HUVEC had been incubated with ET to PRP produced a decrease in PRP aggregation, [TXA2], and [Ca++]i, and an increase not only in [cAMP]i but also in [cGMP]i in platelets. In the HUVEC pretreated with acetylsalicylic acid (aspirin), this increase of [cGMP]i was not affected, but the HUVEC-mediated decrease in PRP aggregation, [TXA2], and [Ca++]i induced by ET were not completely abolished. However, the pretreatment of HUVEC with a combination of aspirin and L-NG-monomethyl arginine (LNMMA) as an inhibitor of EDRF completely abolished the HUVEC-mediated decrease in PRP aggregation, [TXA2] and [Ca++]i induced by ET, and also abolished the enhancement of [cGMP]i and [cAMP]i in platelets. The PGI2 of HUVEC was enhanced by ET with no changes in [Ca++]i, [cAMP]i and [cGMP]i. The ET-induced enhancement was remarkably attenuated by pretreating the HUVEC with aspirin, but not with LNMMA. We conclude that ET attenuates the aggregation of platelets through a decrease in [TXA2] by an increase in [cAMP]i via the increase in PGI2 of HUVEC, and by an increase in [cGMP]i via EDRF.
authors.affiliation: Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Sawada
authors.forename: T
authors.initials: T
authors.lastname: Toyoda
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Shirai
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Tamagaki
authors.forename: M
authors.initials: M
authors.lastname: Yamagami
authors.forename: M
authors.initials: M
authors.lastname: Yoneda
authors.forename: O
authors.initials: O
authors.lastname: Takada
mesh_terms: D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010974:Platelet Aggregation; D013928:Thromboxane A2 / Q000096:biosynthesis; D014471:Umbilical Veins
chemical_list: D016232:Endothelins; D009569:Nitric Oxide; D013928:Thromboxane A2; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium