Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats
Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats
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DOI：
10.1038/sj.bjp.0704300
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发表时间：
2001-10-01
影响因子：
7.3
通讯作者：
Kunitomo, M
中科院分区：
文献类型：
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作者：
Kagota, S;Tamashiro, A;Kunitomo, M
1环磷酸鸟苷（cyclicguanosinemonophosphate，cGMP）介导的机制在血管舒张和血压调节中起重要作用。我们研究了高盐摄入对调节自发性高血压大鼠（SHR）血管舒张的一氧化氮（NO）-环磷酸鸟苷（cGMP）信号转导通路的影响。2 4周龄SHR和血压正常的Wistar-Kyoto大鼠（WKY）接受正常盐饮食（0.3%NaCl）或高盐饮食（8%NaCl）4周。3在SHR的主动脉环中，腺苷二磷酸（ADP）和钙离子载体A23187显着受损的高盐摄入量。硝普钠（SNP）和硝酸甘油的内皮非依赖性舒张反应也受损，但8-溴环GMP保持不变。另一方面，高盐饮食对WKY大鼠主动脉环的舒张作用无显著影响。4在SHR大鼠主动脉中，高盐摄入显著增加了ACh刺激的NO释放，而降低了ACh或SNP诱导的cGMP产生。5 Western blot分析显示，内皮型一氧化氮合酶（eNOS）蛋白水平略有增加，而可溶性鸟苷酸环化酶（sGC）的含量因高盐摄入而显着降低。6这些结果表明，在SHR中，过量的膳食盐会导致sGC下调，随后导致环GMP产生减少，这导致血管舒张对NO的反应受损。值得注意的是，慢性高盐摄入会损害sGC/环GMP途径，而不是eNOS/NO途径。
1 Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an important role in vasodilatation and blood pressure regulation. We investigated the effects of high salt intake on the nitric oxide (NO)-cyclic GMP signal transduction pathway regulating relaxation in aortas of spontaneously hypertensive rats (SHR).2 Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a normal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks.3 In aortic rings from SHR, endothelium-dependent relaxations in response to acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A23187 were significantly impaired by the high salt intake. The endothelium-independent relaxations in response to sodium nitroprusside (SNP) and nitroglycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchanged. On the other hand, high salt diet had no significant effects on the relaxations of aortic rings from WKY.4 In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SNP was decreased by the high salt intake.5 Western blot analysis showed that the protein level of endothelial NO synthase (eNOS) was slightly increased, whereas that of soluble guanylate cyclase (sGC) was dramatically reduced by the high salt intake.6 These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which leads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not the eNOS/NO pathway.