P4482Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers

Abstract

Abstract Background/Introduction Hypertension is highly prevalent in NAFLD patients (39%). NAFLD has been independently associated with an increased risk of arterial hypertension in observational studies and emerge as the most frequent cause of chronic hepatic disease in adults. Therefore, we can deduce that treating hypertension in NAFLD carriers will be often necessary. However, there are no established criteria for choosing the most appropriate drug therapy for hypertension in patients with NAFLD, and the basic research may be the first step to the development of these criteria. Purpose We aimed to evaluate the effects of the renin-angiotensin system blockade with angiotensin-converting enzyme inhibitor ramipril and angiotensin 2 type 1 receptor antagonist olmesartan, used preventively, in NAFLD induced in rabbits fed hypercholesterolemic diet. Antihypertensive drugs in experimental NAFLD as the first step to the establishment of criteria for choosing appropriate treatment of hypertension in NAFLD carriers. Methods Olmesartan study: Thirty-four rabbits were divided into three groups (control, untreated and olmesartan). The untreated and olmesartan group were fed a hypercholesterolemic diet. Animals from olmesartan group were treated with olmesartan 1mg/kg/day. Ramipril study: Twenty-nine rabbits were divided into three groups (normal, placebo, and ramipril). The placebo and ramipril groups were fed a hypercholesterolemic diet. The groups were orally administered 0.35 mg/kg/day of ramipril, and an equivalent volume of vehicle was administered to the placebo group. In both studies, at the end of the 8th week, all rabbits underwent segmental hepatic resection and were euthanised. Blood samples were collected to determine glucose, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and aminotransferase levels at baseline and euthanasia. Haematoxylin and eosin and Gomori trichrome stained slides were analysed based on the histological scoring system for NAFLD. Results The comparison between two groups (olmesartan with untreated group and ramipril with placebo) showed that ramipril and olmesartan significantly diminished the development of steatosis (p<0.013, p=0.032), lobular inflammation (p<0.001, p=0.006), and fibrosis (p=0.015, p=0.02). Based on NAFLD activity score, olmesartan and ramipril significantly reduced the development of nonalcoholic steatohepatitis (p<0.001, p=0.003). Conclusion(s) The preventive use of olmesartan and ramipril attenuates the development of hepatic steatosis, lobular inflammation and fibrosis in hypercholesterolemic rabbits. These results can serve as the basis to the establishment of criteria for choosing the most appropriate drug therapy for hypertension in NAFLD carriers.