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. © the japanese pharmacological society.