title: Vascular smooth muscle contractility assays for inflammatory and immunological mediators.
abstract: The blood vessels are one of the important target tissues for the mediators of inflammation and allergy; further cytokines affect them in a number of ways. We review the use of the isolated blood vessel mounted in organ baths as an important source of pharmacological information. While its use in the bioassay of vasoactive substances tends to be replaced with modern analytical techniques, contractility assays are effective to evaluate novel synthetic drugs, generating robust potency and selectivity data about agonists, partial agonists and competitive or insurmountable antagonists. For instance, the human umbilical vein has been used extensively to characterize ligands of the bradykinin B(2) receptors. Isolated vascular segments are live tissues that are intensely reactive, notably with the regulated expression of gene products relevant for inflammation (e.g., the kinin B(1) receptor and inducible nitric oxide synthase). Further, isolated vessels can be adapted as assays of unconventional proteins (cytokines such as interleukin-1, proteases of physiopathological importance, complement-derived anaphylatoxins and recombinant hemoglobin) and to the gene knockout technology. The well known cross-talks between different cell types, e.g., endothelium-muscle and nerve terminal-muscle, can be extended (smooth muscle cell interaction with resident or infiltrating leukocytes and tumor cells). Drug metabolism and distribution problems can be modeled in a useful manner using the organ bath technology, which, for all these reasons, opens a window on an intermediate level of complexity relative to cellular and molecular pharmacology on one hand, and in vivo studies on the other.
authors.affiliation: Centre de recherche en rhumatologie et immunologie, Centre Hospitalier Universitaire de Québec, Québec, QC, Canada. francois.marceau@crchul.ulaval.ca
authors.forename: François
authors.initials: F
authors.lastname: Marceau
authors.forename: Denis
authors.initials: D
authors.lastname: deBlois
authors.forename: Eric
authors.initials: E
authors.lastname: Petitclerc
authors.forename: Luc
authors.initials: L
authors.lastname: Levesque
authors.forename: Guy
authors.initials: G
authors.lastname: Drapeau
authors.forename: Ritchie
authors.initials: R
authors.lastname: Audet
authors.forename: Denis
authors.initials: D
authors.lastname: Godin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Larrivée
authors.forename: Steeve
authors.initials: S
authors.lastname: Houle
authors.forename: Thierry
authors.initials: T
authors.lastname: Sabourin
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Fortin
authors.forename: Guillaume
authors.initials: G
authors.lastname: Morissette
authors.forename: Lajos
authors.initials: L
authors.lastname: Gera
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Bawolak
authors.forename: Gérémy Abdull
authors.initials: GA
authors.lastname: Koumbadinga
authors.forename: Johanne
authors.initials: J
authors.lastname: Bouthillier
mesh_terms: D000818:Animals; D001681:Biological Assay; D001808:Blood Vessels / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects* / Q000276:immunology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D009924:Organ Culture Techniques; D010447:Peptide Hydrolases / Q000032:analysis / Q000276:immunology; D051381:Rats; D043782:Receptor, Bradykinin B2 / Q000032:analysis / Q000276:immunology; D014471:Umbilical Veins / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D043782:Receptor, Bradykinin B2; D052247:Nitric Oxide Synthase Type II; D010447:Peptide Hydrolases