Effects of Angiotensin II AT1–Receptor Blockade on High Fat Diet–Induced Vascular Oxidative Stress and Endothelial Dysfunction in Dahl Salt-Sensitive Rats

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 p22phox and gp91phox 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.