In salt-sensitive hypertension, increased superoxide production is linked to functional upregulation of angiotensin II
In salt-sensitive hypertension, increased superoxide production is linked to functional upregulation of angiotensin II
复制标题
DOI：
10.1161/01.hyp.0000094220.06020.c8
复制
发表时间：
2003-11-01
期刊：
影响因子：
8.3
通讯作者：
Raij, L
中科院分区：
文献类型：
--
作者：
Zhou, MS;Adam, AG;Raij, L
内皮型一氧化氮（NO）和血管紧张素II（Ang II）之间的平衡维持心血管和肾脏系统的稳态。我们测试的假设，增加氧化应激与NO和血管紧张素II之间的功能失衡可能发挥中央发病机制的作用，盐敏感性（SS）高血压。我们研究了达尔SS（DS）大鼠在高盐（4%NaCl）饮食的高血压前期（5天）和高血压（12周）阶段。对照组大鼠接受正常盐（0.5%NaCl，[NS]）饮食。高血压前DS大鼠（收缩压[SBP] 138 +/- 2 mm Hg）显示主动脉超氧化物（O-2（-））产生增加35%（P < 0.05），而无终末器官损伤的证据。高血压DS大鼠（SBP 214 +/- 11 mm Hg）的内皮依赖性舒张功能（EDR）受损，主动脉O-2（-）生成（320%）、尿异前列腺素排泄（83%）、主动脉（20%）和左心室（LVH，21%）肥大和蛋白尿（124%）增加。在高血压前DS大鼠中，坎地沙坦（10 mg . kg（-1）。d（-1））Ang II 1型受体阻断剂（ARB），使O-2（-）产生正常化。在高血压DS大鼠中，ARB使主动脉O-2（-）产生减少71%，并使EDR正常化，而不影响SBP（212 +/- 8 mm Hg）、主动脉肥大、LVH或蛋白尿。将高血压DS大鼠转换为NS饮食不影响SBP（208 +/- 8 mm Hg）、LVH、主动脉肥大或蛋白尿，对O-2（-）和EDR的影响极小。伴随ARB给药加上转换为NS饮食使SBP（138 +/- 8 mm Hg）以及终末器官损伤正常化。Dahl耐盐大鼠喂食HS饮食12周，没有表现出高血压或O-2（-）产生增加。因此，SS高血压可能代表一种特定的血管素质，与Ang II作用的功能性上调（增加O-2（-）合成）相关，伴有NO生物利用度不足，从而促进严重的内皮功能障碍。
The balance between endothelial nitric oxide (NO) and angiotensin II (Ang II) maintains the homeostasis of the cardiovascular and renal systems. We tested the hypothesis that increased oxidant stress linked to a functional imbalance between NO and Ang II might play a central pathogenetic role in salt-sensitive (SS) hypertension. We studied Dahl SS (DS) rats during the prehypertensive (5 days) and hypertensive (12 weeks) phases of a high-salt (4% NaCl) diet. Control rats received a normal-salt (0.5% NaCl, [NS]) diet. Prehypertensive DS rats (systolic blood pressure [SBP] 138 +/- 2 mm Hg) manifested a 35% increase (P < 0.05) in aortic superoxide (O-2(-)) production without evidence of end-organ damage. Hypertensive DS rats (SBP 214 +/- 11 mm Hg) had impaired endothelium-dependent relaxation (EDR) and increased aortic O-2(-) production (320%), urinary isoprostane excretion (83%), aortic (20%) and left ventricular (LVH, 21%) hypertrophy, and proteinuria (124%). In prehypertensive DS rats, candesartan (10 mg . kg(-1) . d(-1)) an Ang II type 1 receptor blocker (ARB), normalized O-2(-) production. In hypertensive DS rats, the ARB decreased aortic O-2(-) production by 71% and normalized EDR without affecting SBP (212 +/- 8 mm Hg), aortic hypertrophy, LVH, or proteinuria. Switching hypertensive DS rats to an NS diet did not affect SBP (208 +/- 8 mm Hg), LVH, aortic hypertrophy, or proteinuria and had minimal effects on O-2(-) and EDR. Concomitant ARB administration plus a switch to an NS diet normalized SBP (138 +/- 8 mm Hg) as well as end-organ damage. Dahl salt-resistant rats fed an HS diet for 12 weeks did not show hypertension or increased O-2(-) production. Thus, SS hypertension might represent a specific vascular diathesis linked to functional upregulation of Ang II action (increased O-2(-) synthesis) accompanied by insufficient NO bioavailability, which promotes severe endothelial dysfunction.