Effect of glucocorticoids, monokines and growth factors on the spontaneously developing responses of the rabbit isolated aorta to des-Arg9-bradykinin.
1. The mechanisms modulating the spontaneous induction of contractile responses to agonists of the B1-receptors for kinins have been studied by submitting the rabbit isolated aorta preparation to various in vitro treatments. Des-Arg9-bradykinin (Des-Arg9-BK), applied after 6 h of in vitro incubation was the standard stimulus to monitor this up-regulation process. 2. Specific inhibition of the development of the contractile response to des-Arg9-BK was obtained by exposing tissues continuously to dexamethasone, dexamethasone sodium phosphate (DSP) or cortisol, but not to oestradiol. The maximal extent of the inhibition obtained at high concentrations of glucocorticoids was 86%. 3. No gross inhibition of protein synthesis was observed in the presence of DSP as monitored by [35S]-methionine incorporation into incubated pieces of rabbit aorta. 4. In vivo pretreatment of rabbits with DSP did not reduce further the development of the responses in vitro. DSP applied 15 min before the 6 h recording did not antagonize the contractile effect of the BK fragment. 5. Interleukin 1 (IL-1) and interleukin 2 (IL-2) applied in vitro for the first 3 h of incubation increased the development of the contractile response to des-Arg9-BK. 6. Arachidonic acid (AA), nordihydroguaiaretic acid, tumour necrosis factor-alpha (TNF) and transforming growth factor-beta (TGF-beta) failed to influence the spontaneous development of the response to kinins. 7. Continuous exposure to DSP (100 microM) markedly inhibited the action of stimulants in this system: IL-1, IL-2, epidermal growth factor and muramyl dipeptide. Moreover, the presence of AA (30 microM) did not prevent the inhibitory effect of DSP (100 microM). 8. None of the treatments applied singly or in combination modified the contractile response of the rabbit aorta to noradrenaline. 9. The results are discussed in terms of the possible involvement of immunocompetent cells in the up-regulation of vascular responsiveness to B, receptor agonists.
Deblois
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Unité de recherche Inflammation et Immuno-Rhumatologie, Centre Hospitalier de l'Université Laval, Québec, Canada.
Bouthillier
J
J
Marceau
F
F
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D066298:In Vitro Techniques; D008715:Methionine / Q000378:metabolism; D015846:Monokines; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D013462:Sulfur Radioisotopes
D001688:Biological Products; D005938:Glucocorticoids; D006133:Growth Substances; D015846:Monokines; D013462:Sulfur Radioisotopes; C024626:bradykinin, des-Arg(9)-; D008715:Methionine; D001920:Bradykinin; D009638:Norepinephrine