This study examined the effects of interleukin-1β on isometric tension development and relaxation in isolated rat aortic rings in response to the α-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-1β to cause early arterial endothelial dysfunction. Paired aortic rings were incubated for 2 hrs with interleukin-1β or vehicle. Series II examined the potential for inhibition of DNA transcription to attenuate interleukin-1β-mediated endothelial dysfunction. Paired rings received either dactinomycin or vehicle before interleukin-1β incubation. Series III quantified the degree to which inhibition of DNA transcription inhibited early interleukin-1β-mediated endothelial dysfunction. Paired rings received either dactinomycin pretreatment followed by interleukin-1β incubation, or pretreatment and incubation with inert vehicles. Series IV assessed the effects of interleukin-1β on responsiveness to an exogenous nitric oxide donor, sodium nitroprusside, in the presence of the nitric oxide synthesis inhibitor Nω-nitro-L-arginine methyl ester.Measurements and Main Results
Incubation with interleukin-1β for 2 hrs had no effect on contractile response but attenuated endothelium-dependent relaxation significantly relative to control. Dactinomycin pretreatment inhibited early interleukin-1β-mediated endothelial dysfunction. The combination of interleukin-1β and dactinomycin produced effects on endothelium-dependent relaxation that were not different from that seen in rings not exposed to interleukin-1β. Interleukin-1β attenuated responsiveness to sodium nitroprusside relative to control.Conclusions
Interleukin-1β 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-1β is at least partly mediated by a reduction in nitric oxide responsiveness.