血胆甾醇过多的关系,内皮功能障碍和高血压。
文章的细节
-
引用
复制到剪贴板 -
Hayakawa H, Raij L
血胆甾醇过多的关系,内皮功能障碍和高血压。
J Hypertens。1999年5月,17 (5):611 - 9。
- PubMed ID
-
10403604 (在PubMed]
- 文摘
-
目标:我们曾表明,大鼠高胆固醇的饮食和缺乏维生素E和硒导致血胆甾醇过多,增加脂质氧化。我们利用这个模型来确定大鼠鉴于这种饮食发展受损endothelium-dependent放松由一氧化氮(NO)在肠系膜和肾脏血管。此外,我们测试是否损伤是由于(i)减少内皮没有合酶活动,(2)增加没有失活和/或(3)增加产量的endothelium-derived压缩因子血栓素A2 /前列腺素H2和endothelin-1。我们也调查了dyslipidaemia引起的内皮功能障碍是否增加了敏感性高血压的发展在应对高盐饮食。方法:男性达尔食盐过敏(DSS)老鼠分成了三组,接受了标准的饮食(对照组),高(4%)胆固醇的饮食(HChol),或高胆固醇饮食缺乏抗氧化剂维生素E和硒(HChol-Def)。这些饮食的氯化钠含量为0.5%。18周后我们研究endothelium-dependent放松针对乙酰胆碱(ACh)在主动脉和肠系膜动脉模型包括准备和肾脏。在一些实验,ifetroban血栓素A2 /前列腺素H2受体拮抗剂,添加到器官浴或灌注缓冲区。血管反应endothelin-1 bq - 123、内皮素受体阻断剂,研究了在模型包括肾脏。此外,两个组的老鼠喂食高氯化钠的饮食(2%):一个组织获得了正常胆固醇饮食而另一组获得了高胆固醇的饮食和缺乏维生素E和硒。 RESULTS: Compared to normocholesterolemic rats, responses to ACh were significantly impaired in aortas, mesenteric arteries and kidneys of HChol-Def rats (P < 0.01). Endothelial NO synthase activity (conversion of [14C]L-arginine to [14C]L-citrulline) was similar in aortas of control, HChol and HChol-Def rats; thus suggesting that impaired endothelium-dependent relaxation in the HChol-Def rats was not due to decreased cNOS catalytic activity. Ifetroban improved the impaired endothelium-dependent relaxation in mesenteric vessels, but not in aortas and kidneys. Endothelin-1 (ET-1: 10(-13)-10(-11) mol/l) elicited NO-mediated relaxations in kidneys of control rats but not in kidneys of HChol-Def; blockade of ET-1 with BQ-123, an ET(A) receptor blocker, did not improve NO-mediated relaxation of HChol-Def. Despite impaired endothelium-dependent relaxation in renal and mesenteric vessels, HChol-Def DSS rats failed to develop hypertension (systolic blood pressure 144 +/- 1 in control and 150 +/- 2 mmHg in HChol-Def) but manifested a significant increase in sensitivity to the pressor effects of a high (2% NaCl) dietary salt content during the initial 10 weeks of the study, although the final blood pressure at 18 weeks was similar in both groups. CONCLUSION: These studies support the notion that (i) products of lipid oxidation may reduce NO bioactivity without affecting endothelial NO synthase mass or catalytic activity, (ii) the mechanisms involved in the endothelial dysfunction induced by hypercholesterolaemia and oxidized lipids may differ among vascular beds, and (iii) decreased NO bioavailability does not necessarily result in systemic hypertension, but it may enhance the sensitivity to the hypertensinogenic effect of dietary salt.