Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
J Pharmacol Sci. 2013;121(2):95-102. doi: 10.1254/jphs.12169fp. Epub 2013 Jan 22.
We examined the effects of angiotensin II AT₁-receptor blockade with olmesartan on high fat (HF) diet-induced vascular oxidative stress and endothelial dysfunction in normal salt (NS) diet-fed Dahl salt-sensitive (DSS) rats. Treatment with NS + HF diet (32% crude fat, 0.3% NaCl) for 20 weeks significantly increased blood pressure in DSS rats. NS + HF diet-fed DSS rats also showed higher plasma levels of thiobarbituric acid-reactive substances, aortic superoxide production, and mRNA levels of p22(phox) and gp91(phox) in aortic tissues than NS diet-fed DSS rats. Furthermore, acetylcholine-induced vasorelaxation of aorta from NS + HF diet-fed DSS rats was significantly reduced. In NS + HF diet-fed DSS rats, treatment with olmesartan medoxomil (10 mg/kg per day, p.o.) and hydralazine (25 mg/kg per day, p.o.) similarly decreased blood pressure. However, in these animals, only olmesartan normalized plasma levels of thiobarbituric acid-reactive substances, vascular superoxide in aortic tissues, and acetylcholine-induced vasorelaxation. These data indicate that HF diet-induced hypertension is associated with vascular oxidative stress and endothelial dysfunction in NS diet-treated DSS rats. Inhibition of angiotensin II AT₁ receptors may elicit beneficial effects on HF-induced hypertension and vascular injury in subjects that have genetically enhanced sodium-sensitive blood pressure.
我们研究了血管紧张素 II AT₁受体阻断剂奥美沙坦对正常盐（NS）饮食喂养的 Dahl 盐敏感（DSS）大鼠高脂肪（HF）饮食诱导的血管氧化应激和内皮功能障碍的影响。用 NS + HF 饮食（32%粗脂肪，0.3%NaCl）处理 20 周可显著增加 DSS 大鼠的血压。与 NS 饮食喂养的 DSS 大鼠相比，NS + HF 饮食喂养的 DSS 大鼠的血浆硫代巴比妥酸反应物质、主动脉超氧化物产生以及主动脉组织 p22(phox)和 gp91(phox)的 mRNA 水平也更高。此外，来自 NS + HF 饮食喂养的 DSS 大鼠的乙酰胆碱诱导的血管舒张明显降低。在 NS + HF 饮食喂养的 DSS 大鼠中，奥美沙坦（每天 10 mg/kg，po）和肼屈嗪（每天 25 mg/kg，po）治疗同样降低了血压。然而，在这些动物中，只有奥美沙坦可使血浆硫代巴比妥酸反应物质、主动脉组织中的血管超氧化物和乙酰胆碱诱导的血管舒张恢复正常。这些数据表明，HF 饮食诱导的高血压与 NS 饮食治疗的 DSS 大鼠中的血管氧化应激和内皮功能障碍有关。血管紧张素 II AT₁受体的抑制可能对具有遗传增强的钠敏感血压的 HF 诱导的高血压和血管损伤产生有益的影响。
