Effects of Atorvastatin, Amlodipine, and Their Combination on Vascular Dysfunction in Insulin-Resistant Rats

Journal of Pharmacological Sciences

Kazuya Shinozaki²  Yuichi Yoshida³  Ayman Geddawy²  Haruo Shintaku¹  Tomio Okamura²  Hirotaka Iwasaki²  Masashi Tawa²  Takashi Shimosato²  Takeshi Imamura²  Masahiro Masada³ 

[1] Department of Pediatrics, Osaka City University Graduate School of Medicine, Japan;Department of Pharmacology, Shiga University of Medical Science, Japan;Laboratory of Biochemistry, Faculty of Horticulture, Chiba University, Japan

关键词: 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor;    calcium antagonist;    nitric oxide;    tetrahydrobiopterin;    insulin resistance;   

DOI  :  10.1254/jphs.13178FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(41)Cited-By(6)Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endothelial dysfunction through reduced eNOS activity and increased superoxide anion (O2�?) generation in the insulin-resistant state. We investigated the effects of atorvastatin, a 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor; amlodipine, a calcium antagonist; and their combination on blood pressure, arterial relaxation and contraction, and vascular oxidative stress in aortas of high fructose–fed rats. Oral administration of atorvastatin for 8 weeks did not significantly lower blood pressure, but normalized angiotensin II–induced vasoconstriction and endothelial function in the fructose-fed rats. Atorvastatin treatment of fructose-fed rats increased vascular BH4 content, which was associated with an increase in endothelial NO synthase activity as well as a reduction in endothelial O2�? production. On the other hand, administration of amlodipine did not affect the angiotensin II–induced vasoconstriction and endothelial function, but normalized the elevated blood pressure in the fructose-fed rats. The combined treatment did not show synergistic but additive beneficial effects. The present study suggests that combined therapy of HMG-CoA reductase inhibitors and calcium antagonists prevents functional vascular disorders in the insulin-resistant state, possibly resulting in the protection against or delay of development of hypertension, vascular dysfunction in diabetes, and thereafter atherosclerosis.

【 授权许可】

Unknown