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大鼠尾端延髓腹外侧区二氧化硫通过谷氨酸受体及NOS/cGMP信号途径产生心血管抑制效应

蔡红燕¹, 李斌², 党磊², 杨静¹, 满珂¹, 董晨明¹, 鲁彦^3,*

¹兰州大学第二医院重症医学科，兰州 730000；²兰州大学第一医院普外科、介入放射科，兰州 730000；³甘肃省人民医院检验科，兰州 730000

摘要

本研究旨在探讨二氧化硫(SO2)在麻醉大鼠尾端延髓腹外侧区(caudal ventrolateral medulla, CVLM)的心血管效应及其机制。在CVLM单侧及双侧微量注射不同剂量SO2 (2, 20, 200 pmol)或人工脑脊液(artificial cerebrospinal fluid, aCSF)，观察SO2对大鼠血压和心率产生的影响；在CVLM预先注射不同信号途径阻断剂，观察其对SO2引起血压和心率变化的影响。结果显示，在CVLM单侧或双侧微量注射SO2产生了剂量依赖性血压下降及心率减慢(P < 0.01)。双侧注射微量SO2 (2 pmol)引起血压降低的幅度比单侧注射时更大(P < 0.01)。在CVLM预先注射谷氨酸受体拮抗剂犬尿喹啉酸(kynurenic acid, Kyn, 5 nmol)或可溶性鸟苷酸环化酶(soluble guanylate cyclase, sGC)抑制剂1H-[1, 2, 4]噁二唑[4, 3-a]喹喔啉-1-酮(ODQ, 1 pmol)均显著减弱SO2的血压降低(P < 0.01)及心率减慢(P < 0.01)效应；在CVLM预注射一氧化氮合酶(nitric oxide synthase, NOS)抑制剂NG-硝基-L-精氨酸甲酯(L-NAME, 10 nmol)可以显著减弱SO2引起的心率减慢效应(P < 0.01)，但对其降低血压的效应无明显影响(P > 0.05)。以上结果提示，SO2在大鼠CVLM具有心血管抑制效应，其机制与谷氨酸受体及NOS/cGMP信号途径有关。

关键词： 血压; 心率; 二氧化硫; 谷氨酸受体; NOS/cGMP信号途径; 尾端延髓腹外侧区

Sulfur dioxide in the caudal ventrolateral medulla reduces blood pressure and heart rate in rats via the glutamate receptor and NOS/cGMP signal pathways

CAI Hong-Yan¹, LI Bin², DANG Lei², YANG Jing¹, MAN Ke¹, DONG Chen-Ming¹, LU Yan^3,*

¹Department of Critical Care, Lanzhou University Second Hospital, Lanzhou 730000, China；²Department of General Surgery, Department of Interventional Radiology, The First Hospital of Lanzhou University, Lanzhou 730000, China；³Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou 730000, China

Abstract

This study was designed to investigate the cardiovascular effects of sulfur dioxide (SO2) in the caudal ventrolateral medulla (CVLM) of anesthetized rats and its mechanism. Different doses of SO2 (2, 20, 200 pmol) or artificial cerebrospinal fluid (aCSF) were injected into the CVLM unilaterally or bilaterally, and the effects of SO2 on blood pressure and heart rate of rats were observed. In order to explore the possible mechanisms of SO2 in the CVLM, different signal pathway blockers were injected into the CVLM before the treatment with SO2 (20 pmol). The results showed that unilateral or bilateral microinjection of SO2 reduced blood pressure and heart rate in a dose-dependent manner (P < 0.01). Moreover, compared with unilateral injection of SO2 (2 pmol), bilateral injection of 2 pmol SO2 produced a greater reduction in blood pressure. Local pre-injection of the glutamate receptor blocker kynurenic acid (Kyn, 5 nmol) or soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 pmol) into the CVLM attenuated the inhibitory effects of SO2 on both blood pressure and heart rate. However, local pre-injection of nitric oxide synthase (NOS) inhibitor NG-Nitro-L-arginine methyl ester (L-NAME, 10 nmol) only attenuated the inhibitory effect of SO2 on heart rate but not blood pressure. In conclusion, SO2 in rat CVLM has cardiovascular inhibitory effects, and its mechanism is related to the glutamate receptor and NOS/cGMP signal pathways.

Key words: Blood pressure; heart rate; sulfur dioxide; glutamate receptors; NOS/cGMP signal pathway; caudal ventrolateral medulla

收稿日期：　　录用日期：

通讯作者：鲁彦　　E-mail:

DOI: 10.13294/j.aps.2023.0011

引用本文：

蔡红燕, 李斌, 党磊, 杨静, 满珂, 董晨明, 鲁彦. 大鼠尾端延髓腹外侧区二氧化硫通过谷氨酸受体及NOS/cGMP信号途径产生心血管抑制效应[J]. 生理学报 2023; 75 (1): 27-35.

CAI Hong-Yan, LI Bin, DANG Lei, YANG Jing, MAN Ke, DONG Chen-Ming, LU Yan. Sulfur dioxide in the caudal ventrolateral medulla reduces blood pressure and heart rate in rats via the glutamate receptor and NOS/cGMP signal pathways. Acta Physiol Sin 2023; 75 (1): 27-35 (in Chinese with English abstract).