Watanabe T, Sakata Y, Fujioka T, Sadamitsu D, Maekawa T
Department of Physiology and Department of Critical Care and Emergency Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
J Pharmacol Exp Ther. 1999 Apr;289(1):24-30.
We investigated whether changes in nitric oxide (NO) release might be responsible for the modulation by glucocorticoids of the pressor response to i.p. injection of interleukin-1beta (IL-1beta) in freely moving rats. In such rats, IL-1beta (10 microgram/kg) induced a biphasic pressor response, with a rise in the plasma concentration of NOx (NO2(-) and NO3(-): metabolites of NO) during the second phase. Systemic pretreatment with an exogenous glucocorticoid, dexamethasone (0.5 mg/kg), enhanced the second phase of the pressor response and completely suppressed the increase in plasma NOx. Treatment with Nomega-nitro-L-arginine methyl ester (L-NAME, a nonspecific NO synthase inhibitor), enhanced the pressor response while attenuating the increase in plasma NOx. After bilateral adrenalectomy, IL-1beta induced a smaller pressor response, but a larger increase in plasma NOx; dexamethasone reversed these changes. Our results suggest that endogenous NO moderates the pressor response to IL-1beta in freely moving rats, and that glucocorticoids enhance the IL-1beta-induced pressor response at least in part by reducing endogenous NO release.
我们研究了一氧化氮（NO）释放的变化是否可能是糖皮质激素对自由活动大鼠腹腔注射白细胞介素-1β（IL-1β）所致升压反应进行调节的原因。在此类大鼠中，IL-1β（10微克/千克）诱发双相升压反应，在第二阶段期间血浆NOx（NO2⁻和NO3⁻：NO的代谢产物）浓度升高。用外源性糖皮质激素地塞米松（0.5毫克/千克）进行全身预处理，增强了升压反应的第二阶段，并完全抑制了血浆NOx的升高。用Nω-硝基-L-精氨酸甲酯（L-NAME，一种非特异性NO合酶抑制剂）处理，增强了升压反应，同时减弱了血浆NOx的升高。双侧肾上腺切除术后，IL-1β诱发的升压反应较小，但血浆NOx升高幅度较大；地塞米松逆转了这些变化。我们的结果表明，内源性NO可减轻自由活动大鼠对IL-1β的升压反应，且糖皮质激素至少部分通过减少内源性NO释放来增强IL-1β诱发的升压反应。
