Vascular smooth muscle contractility assays for inflammatory and immunological mediators.
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.
Marceau
François
F
Centre de recherche en rhumatologie et immunologie, Centre Hospitalier Universitaire de Québec, Québec, QC, Canada. francois.marceau@crchul.ulaval.ca
deBlois
Denis
D
Petitclerc
Eric
E
Levesque
Luc
L
Drapeau
Guy
G
Audet
Ritchie
R
Godin
Denis
D
Larrivée
Jean-François
JF
Houle
Steeve
S
Sabourin
Thierry
T
Fortin
Jean-Philippe
JP
Morissette
Guillaume
G
Gera
Lajos
L
Bawolak
Marie-Thérèse
MT
Koumbadinga
Gérémy Abdull
GA
Bouthillier
Johanne
J
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
D016207:Cytokines; D018836:Inflammation Mediators; D043782:Receptor, Bradykinin B2; D052247:Nitric Oxide Synthase Type II; D010447:Peptide Hydrolases