Interleukin-1β rapidly inhibits aortic endothelium-dependent relaxation by a DNA transcription-dependent mechanism

被引:17
作者
Loughrey, JPR [1 ]
Laffey, JG [1 ]
Moore, BJ [1 ]
Lynch, F [1 ]
Boylan, JF [1 ]
McLoughlin, P [1 ]
机构
[1] Univ Coll Dublin, Dept Physiol, Dublin 2, Ireland
关键词
interleukin-1; sepsis; alpha 1-adrenergic receptor; acetylcholine; nitroprusside; vascular; dactinomycin;
D O I
10.1097/01.CCM.0000053516.15727.E5
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objectives: This study examined the effects of interleukin-1beta on isometric tension development and relaxation in isolated rat aortic rings in response to the alpha-1 adrenergic agonist phenylephrine, the endothelium-dependent vasodilator acetylcholine, and the endothelium-independent vasodilator sodium nitroprusside. Design: Randomized, controlled, paired design. Setting. Animal laboratory within a university department of physiology. Subjects. Paired ex vivo aortic thoracic aortic rings from specific pathogen-free Sprague-Dawley rats. Interventions: Series I examined the potential for interleukin-1beta to cause early arterial endothelial dysfunction. Paired aortic rings were incubated for 2 hrs with interleukin-1beta or vehicle. Series 11 examined the potential for inhibition of DNA transcription to attenuate interleukin-1beta-mediated endothelial dysfunction. Paired rings received either dactinomycin or vehicle before interleukin-1beta incubation. Series III quantified the degree to which inhibition of DNA transcription inhibited early interleukin-1beta-mediated endothelial dysfunction. Paired rings received either dactinomycin pretreatment followed by interleukin-1beta incubation, or pretreatment and incubation with inert vehicles. Series IV assessed the effects of interleukin-1 0 on responsiveness to an exogenous nitric oxide donor, sodium nitroprusside, in the presence of the nitric oxide synthesis inhibitor Nomega-nitro-L-arginine methyl ester. Measurements and Main Results., Incubation with interleukin-1beta for 2 hrs had no effect on contractile response but attenuated endothelium-dependent relaxation significantly relative to control. Dactinomycin pretreatment inhibited early interleukin-1beta-mediated endothelial dysfunction. The combination of interleukin-1beta and dactinomycin produced effects on endothelium-dependent relaxation that were not different from that seen in rings not exposed to interleukin-1beta. Interleukin-1beta attenuated responsiveness to sodium nitroprusside relative to control. Conclusions., Interleukin-1beta causes an early impairment of endothelium-dependent vasorelaxation with an onset that precedes its effects on systemic contractility. This impairment occurs via a mechanism that is wholly or predominantly dependent on DNA transcription. The altered vasorelaxation induced by interleukin-1beta is at least partly mediated by a reduction in nitric oxide responsiveness.
引用
收藏
页码:910 / 915
页数:6
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