OBJECTIVES: This study examined the effects of interleukin-1 beta 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 aortic thoracic aortic rings from specific pathogen-free Sprague-Dawley rats. INTERVENTIONS: Series I examined the potential for interleukin-1 beta to cause early arterial endothelial dysfunction. Paired aortic rings were incubated for 2 hrs with interleukin-1 beta or vehicle. Series II examined the potential for inhibition of DNA transcription to attenuate interleukin-1 beta-mediated endothelial dysfunction. Paired rings received either dactinomycin or vehicle before interleukin-1 beta incubation. Series III quantified the degree to which inhibition of DNA transcription inhibited early interleukin-1 beta-mediated endothelial dysfunction. Paired rings received either dactinomycin pretreatment followed by interleukin-1 beta incubation, or pretreatment and incubation with inert vehicles. Series IV assessed the effects of interleukin-1 beta on responsiveness to an exogenous nitric oxide donor, sodium nitroprusside, in the presence of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester. MEASUREMENTS AND MAIN RESULTS: Incubation with interleukin-1 beta for 2 hrs had no effect on contractile response but attenuated endothelium-dependent relaxation significantly relative to control. Dactinomycin pretreatment inhibited early interleukin-1 beta-mediated endothelial dysfunction. The combination of interleukin-1 beta and dactinomycin produced effects on endothelium-dependent relaxation that were not different from that seen in rings not exposed to interleukin-1 beta. Interleukin-1 beta attenuated responsiveness to sodium nitroprusside relative to control. CONCLUSIONS: Interleukin-1 beta 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-1 beta is at least partly mediated by a reduction in nitric oxide responsiveness.
OBJECTIVES: This study examined the effects of interleukin-1 beta 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 aortic thoracic aortic rings from specific pathogen-free Sprague-Dawley rats. INTERVENTIONS: Series I examined the potential for interleukin-1 beta to cause early arterial endothelial dysfunction. Paired aortic rings were incubated for 2 hrs with interleukin-1 beta or vehicle. Series II examined the potential for inhibition of DNA transcription to attenuate interleukin-1 beta-mediated endothelial dysfunction. Paired rings received either dactinomycin or vehicle before interleukin-1 beta incubation. Series III quantified the degree to which inhibition of DNA transcription inhibited early interleukin-1 beta-mediated endothelial dysfunction. Paired rings received either dactinomycin pretreatment followed by interleukin-1 beta incubation, or pretreatment and incubation with inert vehicles. Series IV assessed the effects of interleukin-1 beta on responsiveness to an exogenous nitric oxidedonor, sodium nitroprusside, in the presence of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester. MEASUREMENTS AND MAIN RESULTS: Incubation with interleukin-1 beta for 2 hrs had no effect on contractile response but attenuated endothelium-dependent relaxation significantly relative to control. Dactinomycin pretreatment inhibited early interleukin-1 beta-mediated endothelial dysfunction. The combination of interleukin-1 beta and dactinomycin produced effects on endothelium-dependent relaxation that were not different from that seen in rings not exposed to interleukin-1 beta. Interleukin-1 beta attenuated responsiveness to sodium nitroprusside relative to control. CONCLUSIONS:Interleukin-1 beta 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-1 beta is at least partly mediated by a reduction in nitric oxide responsiveness.
Authors: Chrisen H Maharaj; Daniel O'Toole; Tadhg Lynch; John Carney; James Jarman; Brendan D Higgins; John J Morrison; John G Laffey Journal: Reprod Biol Endocrinol Date: 2009-04-23 Impact factor: 5.211
Authors: James Jarman; Chrisen H Maharaj; Brendan D Higgins; Rachel F Farragher; Christopher D Laffey; Noel M Flynn; John G Laffey Journal: BMC Anesthesiol Date: 2009-06-10 Impact factor: 2.217