Direct renin inhibitor prevents and ameliorates insulin resistance, aortic endothelial dysfunction and vascular remodeling in fructose-fed hypertensive rats.
Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers can improve insulin resistance and vascular dysfunction in insulin-resistant rats; however, there are few reports on the effects of direct renin inhibitors on these conditions. We investigated the effects of a direct renin inhibitor, aliskiren, on insulin resistance, aortic endothelial dysfunction and vascular remodeling in fructose-fed hypertensive rats. Male Wistar-Kyoto rats were divided into four groups (n=6 per group) and studied for 8 weeks: Group Con: standard chow diet; group Fru: high-fructose diet (60% fructose); Group FruA: high-fructose diet with concurrent aliskiren treatment (100 mg kg(-1) per day); and Group FruB: high-fructose diet with subsequent aliskiren treatment 4 weeks later. Blood was collected for biochemical assays, and isolated rings of the thoracic aorta were obtained for analysis of vascular reactivity, vascular structure and lipid peroxide. Rats fed with high-fructose diets developed significant systolic hypertension, decreased plasma nitrite (NO(2); nitric oxide metabolite) levels and increased plasma glucose, insulin, triglyceride, total cholesterol and aortic lipid peroxide levels, and aortic wall thickness compared with control rats. Aliskiren treatment, either concurrent or subsequent, elevated plasma NO(2) levels and reduced systolic hypertension, insulin resistance, dyslipidemia, aortic lipid peroxide levels and aortic wall hypertrophy in FHR. The peak endothelium-dependent aortic relaxations were significantly higher in rats that received aliskiren treatment than in those that did not. In conclusion, our findings suggest that aliskiren prevents and ameliorates insulin resistance, aortic endothelial dysfunction and oxidative vascular remodeling in fructose-fed hypertensive rats.
Institute of Medical Sciences, Buddhist Tzu Chi University, Hualien, Taiwan.
Chu-Lin
CL
Chou
Cheng-Yong
CY
Pang
Tony J F
TJ
Lee
Te-Chao
TC
Fang
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005632:Fructose / Q000494:pharmacology*; D005650:Fumarates / Q000494:pharmacology*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*; D007333:Insulin Resistance / Q000502:physiology*; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D000092502:Renin Inhibitors
D000577:Amides; D004040:Dietary Carbohydrates; D005632:Fructose; D005650:Fumarates; D008054:Lipid Peroxides; D009573:Nitrites; D000092502:Renin Inhibitors; C446481:aliskiren