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

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

本研究旨在探讨二氧化硫(SO_(2))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SO_(2) (2, 20, 200 pmol)或人工脑脊液(artificial cerebrospinal fluid, aCSF),观察SO_(2)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SO_(2)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SO_(2)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SO_(2) (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SO_(2)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SO_(2)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,SO_(2)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。

This study was designed to investigate the cardiovascular effects of sulfur dioxide(SO_(2)) in the caudal ventrolateral medulla(CVLM) of anesthetized rats and its mechanism. Different doses of SO_(2)(2, 20, 200 pmol) or artificial cerebrospinal fluid(aCSF) were injected into the CVLM unilaterally or bilaterally, and the effects of SO_(2)on blood pressure and heart rate of rats were observed. In order to explore the possible mechanisms of SO_(2)in the CVLM, different signal pathway blockers were injected into the CVLM before the treatment with SO_(2)(20 pmol). The results showed that unilateral or bilateral microinjection of SO_(2)reduced blood pressure and heart rate in a dose-dependent manner(P < 0.01). Moreover, compared with unilateral injection of SO_(2)(2 pmol), bilateral injection of 2 pmol SO_(2)produced a greater reduction in blood pressure. Local pre-injection of the glutamate receptor blocker kynurenic acid(Kyn, 5nmol) 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 SO_(2)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 SO_(2)on heart rate but not blood pressure. In conclusion, SO_(2)in rat CVLM has cardiovascular inhibitory effects, and its mechanism is related to the glutamate receptor and NOS/cGMP signal pathways.