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Effect of 17β‐oestradiol on cytokine‐induced nitric oxide production in rat isolated aorta
Author(s) -
Kauser Katalin,
Sonnenberg Dagmar,
Diel Patrick,
Rubanyi Gabor M.
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701715
Subject(s) - phenylephrine , nitric oxide , nitric oxide synthase , endocrinology , medicine , nitrite , cycloheximide , chemistry , cytokine , incubation , biology , biochemistry , protein biosynthesis , nitrate , organic chemistry , blood pressure
1 Studies were performed on isolated aortic rings without endothelium to investigate the effect of 17β‐oestradiol on cytokine‐induced nitric oxide production by the inducible nitric oxide synthase (iNOS). 2 Treatment of the isolated aortic rings with interleukin‐1β (IL‐1β, 20 μ ml −1 ) led to the expression of iNOS mRNA and protein, as well as significant nitrite accumulation in the incubation media and suppression of phenylephrine (1 n M –10 μ M )‐evoked contraction. 3 Cycloheximide (1 μ M ), a protein synthesis inhibitor, prevented iNOS protein expression, nitrite accumulation and the suppression of contractility by IL‐1β on the isolated aortic rings. 17β‐oestradiol (1 n M –10 μ M ) and the partial oestrogen receptor agonist 4‐OH‐tamoxifen (1 n M –10 μ M ) produced concentration‐dependent inhibition of IL‐1β‐induced nitrite accumulation and restored vasoconstrictor responsiveness to phenylephrine, similar to the iNOS inhibitor aminoguanidine (100 μ M ). 4 Semiquantitative PCR demonstrated decreased iNOS mRNA in the IL‐1β‐induced and 17β‐oestradiol‐treated rings. Western blot analysis of rat aorta homogenates revealed that 17β‐oestradiol treatment resulted in a reduction in IL‐1ß‐induced iNOS protein level. 5 Incubation with tumour necrosis factor α (TNFα, 1 ng ml −1 ) resulted in significant nitrite accumulation in the incubation media and suppression of the smooth muscle contractile response to phenylephrine, similar to IL‐1β. The effects of TNFα were also inhibited by co‐incubation of the rings with 17β‐oestradiol and 4‐OH‐tamoxifen (1 μ M ). 6 The anti‐transforming growth factor‐β1 (TGF‐β1) antibody, which inhibited TGF‐β1‐induced suppression of nitrite production from IL‐1β‐treated vascular rings, did not affect the inhibitory action of 17β‐oestradiol, suggesting that the effect of oestrogen on iNOS inhibition was not mediated by TGF‐β1. 7 These results show that the ovarian sex steroid, 17β‐oestradiol is a modulator of cytokine‐induced iNOS activity in rat vascular smooth muscle and its mechanism of action involves decrease of iNOS mRNA and protein.British Journal of Pharmacology (1998) 123 , 1089–1096; doi: 10.1038/sj.bjp.0701715