title: Vascular contractile potency of endothelin-1 is increased in the presence of monocytes or macrophages.
abstract: Accumulation of inflammatory cells and altered responsiveness to vasoactive mediators are commonly observed events in atherosclerotic vessels. We studied the effect of monocytic cells on endothelin-1 (ET-1)-induced contraction of strips of guinea pig carotid artery. The vascular contractile potency of ET-1 was increased markedly in the presence of human peripheral blood monocytes, guinea pig alveolar macrophages (M phi), and the human monocytic cell line, THP-1. Specific binding of 125I-labeled ET-1 to these cells was detected, and Scatchard analysis indicated a dissociation constant value of approximately 1 nM. In contrast, the human monocytic cell line, U-937, failed to bind 125I-ET-1 and did not alter ET-1 potency, suggesting that the ability of monocytic cells to increase ET-1 potency requires expression of ET receptors. Selective inhibition of ET-1 binding to vascular smooth muscle with BQ-123, an ETA receptor antagonist that does not inhibit ET-1 binding to monocytes, resulted in complete inhibition of vascular contraction. These data indicate that ET-1-induced vasoconstriction may be increased by monocytic cells via stimulation of monocyte endothelin receptors.
authors.affiliation: Department of Biology, Queens College, City University of New York, Flushing 11367.
authors.forename: H I
authors.initials: HI
authors.lastname: Magazine
authors.forename: T T
authors.initials: TT
authors.lastname: Andersen
authors.forename: C A
authors.initials: CA
authors.lastname: Bruner
authors.forename: A B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects; D002460:Cell Line; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D005404:Fixatives / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D005404:Fixatives; D010456:Peptides, Cyclic; D011108:Polymers; D017382:Reactive Oxygen Species; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D005557:Formaldehyde; D016718:Arachidonic Acid; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C003043:paraform