Chemical stimulation of kidney causes sympathetic activation and pressor responses in rats. The excitatory renal reflex (ERR) is mediated by angiotensin type 1 receptor (AT₁R) and superoxide anions in hypothalamic paraventricular nucleus (PVN). The aim of this study is to determine whether interleukin-1β (IL-1β) in the PVN mediates the ERR, and whether the IL-1β production in the PVN is dependent on the AT₁R-superoxide anion signaling. Experiments were performed in adult rats under anesthesia. The ERR was induced by renal infusion of capsaicin, and evaluated by the responses of the contralateral renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). Inhibition of IL-1β production with MCC950 in the PVN dose-dependently inhibited the capsaicin-induced ERR and sympathetic activation. The PVN microinjection of IL-1 receptor antagonist IL-1Ra or specific IL-1β antibody abolished the capsaicin-induced ERR, while IL-1β enhanced the ERR. Renal infusion of capsaicin promoted p65-NFκB phosphorylation and IL-1β production in the PVN, which were prevented by PVN microinjection of NADPH oxidase inhibitor apocynin or the superoxide anion scavenger tempol. The PVN microinjection of NFκB inhibitor BMS-345541 abolished the capsaicin induced-ERR and IL-1β production, but not the NADPH oxidase activation and superoxide anion production. Furthermore, capsaicin-induced p65-NFκB phosphorylation and IL-1β production in the PVN were prevented by AT₁R antagonist losartan, or angiotensin converting enzyme inhibitor captopril. These results indicate that capsaicin-induced ERR and sympathetic activation are mediated by IL-1β in the PVN. The IL-1β production in the PVN is dependent on the AT₁R-mediated superoxide anion generation and NFκB activation.

肾脏的化学刺激导致大鼠交感神经激活和升压反应。兴奋性肾反射 (ERR) 由血管紧张素 1 型受体 (AT ₁ R) 和下丘脑室旁核 (PVN) 中的超氧阴离子介导。本研究的目的是确定 PVN 中的 IL-1β (IL-1β) 是否介导 ERR，以及 PVN 中 IL-1β 的产生是否依赖于 AT ₁R-超氧阴离子信号。实验是在成年大鼠麻醉下进行的。ERR 由肾脏输注辣椒素诱导，并通过对侧肾交感神经活动 (RSNA) 和平均动脉压 (MAP) 的反应进行评估。在 PVN 中用 MCC950 抑制 IL-1β 产生剂量依赖性地抑制辣椒素诱导的 ERR 和交感神经激活。PVN 显微注射 IL-1 受体拮抗剂 IL-1Ra 或特异性 IL-1β 抗体消除了辣椒素诱导的 ERR，而 IL-1β 增强了 ERR。肾脏输注辣椒素可促进 PVN 中 p65-NFκB 的磷酸化和 IL-1β 的产生，而 PVN 显微注射 NADPH 氧化酶抑制剂夹竹桃素或超氧阴离子清除剂 tempol 可防止这种情况发生。PVN 显微注射 NFκB 抑制剂 BMS-345541 消除了辣椒素诱导的 ERR 和 IL-1β 生成，但不消除 NADPH 氧化酶激活和超氧阴离子生成。此外，辣椒素诱导的 p65-NFκB 磷酸化和 PVN 中 IL-1β 的产生被 AT 阻止₁ R 拮抗剂氯沙坦，或血管紧张素转化酶抑制剂卡托普利。这些结果表明辣椒素诱导的 ERR 和交感神经激活是由 PVN 中的 IL-1β 介导的。PVN 中 IL-1β 的产生取决于 AT ₁ R 介导的超氧阴离子生成和 NFκB 激活。