Deficiency of tetrahydrobiopterin (BH4) in the vascular tissue contributes to endo-thelial 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. © The Japanese Pharmacological Society.
CITATION STYLE
Okamura, T., Tawa, M., Geddawy, A., Shimosato, T., Iwasaki, H., Shintaku, H., … Imamura, T. (2014). Effects of atorvastatin, amlodipine, and their combination on vascular dysfunction in insulin-resistant rats. Journal of Pharmacological Sciences, 124(1), 76–85. https://doi.org/10.1254/jphs.13178FP
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