Hydrogen sulfide defends against the cardiovascular risk of Nw‐nitro‐L‐argininemethyl ester‐induced hypertension in rats via the nitric oxide/endothelial nitric oxide synthase pathway
Hydrogen sulfide defends against the cardiovascular risk of Nw‐nitro‐L‐argininemethyl ester‐induced hypertension in rats via the nitric oxide/endothelial nitric oxide synthase pathway
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DOI：
10.3760/cma.j.issn.0366-6999.20141573
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发表时间：
2014-11
影响因子：
6.1
通讯作者：
Wenqiang Ji;Shangyu Liu;J. Dai;Tao Yang;Xiang-Cheng Jiang;Xiao-cui Duan;Yuming Wu
中科院分区：
文献类型：
--
作者：
Wenqiang Ji;Shangyu Liu;J. Dai;Tao Yang;Xiang-Cheng Jiang;Xiao-cui Duan;Yuming Wu
背景 肝损伤引起的血脂异常是心血管并发症的重要危险因素。先前的研究表明，硫化氢（H2S）以与一氧化氮（NO）类似的方式预防多种心血管疾病状态，而NO/内皮一氧化氮合酶（eNOS）途径是NO产生的关键途径。本研究的目的是探讨 H2S 是否可以通过 NO/eNOS 途径改善 Nw-硝基-L-精氨酸甲酯 (L-NAME) 诱导的高血压大鼠的高血压和血脂水平。方法 36只4周龄SD雄性大鼠随机分为6组（n=6）：对照组、L-NAME组、对照组+格列本脲组、对照组+NaHS组、L-NAME+NaHS组、L-NAME+NaHS+格列本脲组。 5周后测量血浆甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、总胆固醇（CHO）、谷氨酸丙酮转氨酶（ALT）水平。然后测量肝组织中NO水平和eNOS、P-eNOS、AKT、P-AKT蛋白表达。结果 L-NAME治疗5周后，血压、血浆TG（L-NAME组（1.22±0.12）mmol/L vs 对照组（0.68±0.09）mmol/L；P <0.05）、LDL（L-NAME组（0.54±0.04）mmol/L vs 对照组（0.28±0.02）mmol/L；P <0.05）浓度显着升高，L-NAME组血浆HDL（（0.26±0.02）mmol/L vs 对照组（0.69±0.07）mmol/L；P<0.05）浓度显着降低。同时，L-NAME治疗组的大鼠表现出eNOS功能障碍，NO水平降低（L-NAME组为（1.36±0.09）mmol/g蛋白，对照组为（2.34±0.06）mmol/g蛋白；P <0.05）和肝脏病理改变。 H2S治疗可显着降低L-NAME+NaHS组第5周的血压（（37.25±4.46）mmHg；P<0.05），改善血浆TG（（0.59±0.06）mmHg）、LDL（（0.32±0.04）mmHg）和HDL（（0.46±0.03）mmHg）浓度（均P <0.05）。 H2S 治疗还可以恢复 L-NAME 诱导的高血压大鼠的 eNOS 功能和 NO 生物利用度，并减轻肝脏的病理变化。结论 H2S通过NO/eNOS途径保护L-NAME诱导的高血压大鼠免受肝损伤，从而降低心血管风险。
Background Dyslipidemia caused by liver injury is a significant risk factor for cardiovascular complications. Previous studies have shown that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO), and NO/endothelial nitric oxide synthase (eNOS) pathway is the key route of NO production. The purpose of this study was to investigate whether H2S can ameliorate the high blood pressure and plasma lipid profile in Nw‐nitro‐L‐argininemethyl ester (L‐NAME)‐induced hypertensive rats by NO/eNOS pathway. Methods Thirty‐six 4‐week old Sprague‐Dawley (SD) male rats were randomly assigned to 6 groups (n=6): control group, L‐NAME group, control + glibenclamide group, control + NaHS group, L‐NAME + NaHS group, and L‐NAME + NaHS + glibenclamide group. Measurements were made of plasma triglycerides (TG), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), total cholesterol (CHO), glutamic‐pyruvic transaminase (ALT) levels after 5 weeks. Then measurements of NO level and proteins expression of eNOS, P‐eNOS, AKT, P‐AKT were made in liver tissue. Results After 5 weeks of L‐NAME treatment, the blood pressure, plasma TG ((1.22±0.12) mmol/L in L‐NAME group vs. (0.68±0.09) mmol/L in control group; P <0.05) and LDL ((0.54±0.04) mmol/L in L‐NAME group vs. (0.28±0.02) mmol/L in control group; P <0.05) concentration were significantly increased, and the plasma HDL ((0.26±0.02) mmol/L in L‐NAME group vs. (0.69±0.07) mmol/L in control group; P <0.05) concentration significantly decreased. Meanwhile the rats treated with L‐NAME exhibit dysfunctional eNOS, diminished NO levels ((1.36±0.09) mmol/g protein in L‐NAME group vs. (2.34±0.06) mmol/g protein in control group; P <0.05) and pathological changes of the liver. H2S therapy can markedly decrease the blood pressure ((37.25±4.46) mmHg at the fifth week; P <0.05), and ameliorate the plasma TG ((0.59±0.06) mmHg), LDL ((0.32±0.04) mmHg), and HDL ((0.46±0.03) mmHg) concentration in L‐NAME + NaHS group (all P <0.05). H2S therapy can also restore eNOS function and NO bioavailability and attenuate the pathological changes in the liver in L‐NAME‐induced hypertensive rats. Conclusion H2S protects the L‐NAME‐induced hypertensive rats against liver injury via NO/eNOS pathway, therefore decreases the cardiovascular risk.