The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase
The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase
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DOI：
10.1097/00004872-200310000-00015
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发表时间：
2003-10-01
影响因子：
4.9
通讯作者：
Du, JB
中科院分区：
文献类型：
--
作者：
Zhong, GZ;Chen, FR;Du, JB
目的探讨H2S合成酶/H2S通路受损与高血压的关系。方法Wistar大鼠经口给予L-精氨酸类似物N-G-硝基-L-精氨酸甲酯（L-NAME），连续6周。对照组大鼠仅给予普通自来水。对照组和L-NAME治疗组腹腔注射硫氢化钠（NaHS）。收缩压（血压）通过高袖带法使用脉搏传感器测量。测定血浆硫化氢（H2S）以及胸主动脉和上级肠系膜动脉产生的H2S。此外，还测量了胸主动脉和上级肠系膜动脉中胱硫醚-γ-裂解酶（CSE）的活性，这是H2S产生的主要原因。采用竞争性逆转录-聚合酶链反应（RT-PCR）检测CSE mRNA的表达。L-NAME处理组大鼠的心脏与体重比比对照组高27%。NaHS处理的L-NAME组收缩压较L-NAME组显著降低19%（P < 0.01）。心脏-体重比显著降低12%。L-NAME显著抑制CSE基因表达。在NaHS处理的L-NAME组中，L-NAME对H2S生成和CSE活性的抑制作用显著减弱。结论L-NAME诱导的高血压大鼠血管H2S合成酶/H2S途径功能障碍。外源性H2S可有效地阻止L-NAME引起的高血压的发生。这些发现表明H2S合酶/H2S途径参与了（C）2003 Lippincott威廉姆斯威尔金斯。
Objective The present study intended to investigate whether the impaired H2S synthase/H2S pathway is associated with hypertension.Methods Hypertension in Wistar rats was induced by the oral administration of the L-arginine analog, N-G-nitro-L-arginine methyl ester (L-NAME) in their drinking water for period of 6 weeks. The control rats were given plain tap water only. Sodium hydrosulfide (NaHS) was given by intraperitoneal injection to both the control group and the L-NAME-treated group. The systolic BP (blood pressure) was measured by a tall-cuff method using a pulse transducer. Plasma hydrogen sulfide (H2S), and H2S generation by thoracic aorta and superior mesenteric artery, were determined. In addition, the activity of cystathionine-gamma-lyase (CSE) in thoracic aorta and superior mesenteric artery, most responsible for H2S production, was also measured. Competitive reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine CSE mRNA in thoracic aorta.Results L-NAME caused a time-dependent elevation of systolic BP. The heart-to-body weight ratio of L-NAME-treated rats was 27% higher than that of controls. The systolic BP in the NaHS-treated L-NAME group was significantly decreased, by 19% (P < 0.01), in comparison with the L-NAME group. The heart-to-body weight ratio decreased significantly by 12%. L-NAME inhibited CSE gene expression significantly. The inhibition of H2S generation and CSE activity by L-NAME was greatly attenuated in the NaHS-treated L-NAME group. However, there was no significant difference in nitric oxide (NO) generation between the L-NAME group and the NaHS-treated L-NAME group.Conclusion In summary, dysfunction of the vascular H2S synthase/H2S pathway was found in L-NAME-induced hypertensive rats. Exogenous H2S effectively prevented the development of hypertension induced by L-NAME. These findings suggest that the H2S synthase/H2S pathway participates (C) 2003 Lippincott Williams Wilkins.