Effects of interleukin-1 receptor antagonist on three types of responses to interleukin-1 in rabbit isolated blood vessels
| Autor: | E, Petitclerc, S, Abel, D, deBlois, P E, Poubelle, F, Marceau |
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| Rok vydání: | 1992 |
| Předmět: |
Dose-Response Relationship
Drug Muscle Relaxation Sialoglycoproteins Proteins Receptors Interleukin-1 Substance P Bradykinin Recombinant Proteins Mesenteric Arteries Vasodilation Interleukin 1 Receptor Antagonist Protein Norepinephrine Phenylephrine Vasoconstriction Animals Blood Vessels Iloprost Rabbits Receptors Immunologic Interleukin-1 Muscle Contraction |
| Zdroj: | Journal of cardiovascular pharmacology. 19(5) |
| ISSN: | 0160-2446 |
| Popis: | Interleukin-1 receptor antagonist (IRA) is a secretory product of human monocytes or related cell lines that acts as a pure interleukin-1 (IL-1) antagonist in several bioassays. IRA administration was reportedly a life-saving intervention in rabbits injected with lethal doses of bacterial lipopolysaccharide (LPS). We report the inhibitory effect of IRA on three distinct types of vascular responses to IL-1 in rabbit isolated blood vessels. The rabbit isolated superior mesenteric artery, when precontracted with phenylephrine, relaxed in a sustained manner in less than 30 min following application of recombinant interleukin-1 beta (12-290 pM), and this was a prostaglandin (PG)-dependent and endothelium-independent process. IRA (human recombinant sequence; 0.9-15 nM) behaved as an antagonist of IL-1 alpha or IL-1 beta, based on the surmountability and the concentration dependence, but could only prevent the effect of IL-1, not reverse it. IRA had no direct effect on the preparation and did not influence the acute relaxing effect elicited by substance P or iloprost, a PGI2 mimetic. Exposure to IL-1 beta depressed the response to noradrenaline (NA) in several hours in rabbit aorta rings. The inhibitory effect of IL-1 beta was endothelium and prostaglandin independent, but was prevented by a treatment with NG-nitro-L-arginine (a nitric oxide synthesis inhibitor), cycloheximide, dexamethasone, or IRA. Using the residual NA-induced contraction as a quantification of the IL-1 agonist effect, IRA was a very potent antagonist of IL-1 beta but was not totally surmountable.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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